体外震波在缺血缺氧诱导的H9c2细胞凋亡中的作用研究
|
摘要
目的：
大量研究显示细胞凋亡在冠心病的病理生理过程中起着重要的作用。有证据表明,心肌缺血、缺氧、缺血再灌注损伤、氧化应激等因素均可引起心肌及内皮细胞凋亡。多种因素例如氧化应激、缺氧、缺乏生长因子、化学及物理毒性损伤等可通过线粒体及内质网途径的激活而启动细胞凋亡。多项研究报道抑制细胞凋亡可以阻断心衰的发展并改善心功能。体外心脏震波(Cardiac Shock Wave Therapy,CSWT)是目前国际上新近发展起来的前沿科技,可通过上调血管内皮生长因子(VEGF)增加内皮型一氧化氮合酶(eNOS)的活性等途径使缺血区域的毛细血管生成增加,改善该区域心肌灌注。CSWT是否能够减轻缺血缺氧诱导的细胞凋亡目前少有报道,根据国内外目前的研究现状,我们将通过大鼠心肌细胞系H9c2缺血缺氧模型,检测SW对心肌细胞凋亡的影响,并进一步探讨其可能的机制,为缺血性心脏病的治疗提供新的思路。
方法：
选用大鼠心肌细胞来源的细胞系H9c2为研究对象,建立缺血缺氧损伤模型,行不同剂量震波(SW)治疗,观察其对调亡的影响。
1、将H9c2细胞换用无血清培养基,放入含有5%氧气-90%N2-5%C02的三气培养箱中培养,分别缺氧培养12、24、36、48h,MTT方法检测不同时间缺血缺氧对H9c2细胞活力的影响。
2、根据预实验的结果,H9c2细胞缺血缺氧处理24h,建立细胞凋亡模型。分别用Hoechst染色方法及AnnexinV-FITC检测方法检测H9c2细胞凋亡情况,应用流式细胞仪检测H9c2细胞内活性氧产生情况,并检测细胞凋亡相关因子Bax、Bcl-2和Cleaved-Caspase-3的表达情况。
3、H9c2细胞缺血缺氧处理24h后,分别用0.06、0.09、0.12mJ/mm2能量的SW处理细胞,运用MTT方法检测不同能量的SW对H9c2细胞活力的影响。Hoechst染色方法及Annexin V-FITC检测方法检测细胞凋亡并用流式细胞仪检测活性氧产生情况。Western Blot方法检测细胞凋亡相关因子Bax、Bcl-2和Cleaved-Caspase-3及Akt、ERK、p38MAPK信号通路的表达情况。
结果：
1、与对照组相比,缺血缺氧可降低H9c2细胞的细胞活力,并呈现时间依赖性。当缺血缺氧作用时间为24h,细胞活力下降约26%,这是一个中等程度的损伤,不会影响后续的实验结果,因此我们选用缺血缺氧24h作为后续实验处理条件。
2、将H9c2细胞缺血缺氧处理24h后,可以观察到缺血缺氧可诱导H9c2细胞发生凋亡,并且随着时间的延长细胞内活性氧的产生不断增多,Bax、Cleaved-Caspase-3的表达升高而Bcl-2表达下降,证明选择缺血缺氧24h作为处理条件是合适的。
3、为探讨SW对缺血缺氧诱导的H9c2细胞凋亡的作用,分别采用0.06、0.09、0.12mJ/mm2能量的SW处理细胞,实验分为四组,包括正常对照组(NC组)、正常对照+震波组(NC+SW组)、单纯缺血／缺氧组(I/H组)、缺血缺氧+震波组(I/H+SW组)。结果表明,与单纯缺血／缺氧组进行比较,0.06、0.09、0.12mJ/mm2能量SW处理的细胞活力均有明显提高,并有显著的统计学差异,应用0.12mJ/mm2能量SW处理细胞效果最明显。采用流式细胞术检测细胞凋亡情况,结果表明SW可减轻缺血缺氧诱导的H9c2细胞的凋亡,用Hoechest染色方式观察了SW处理对细胞核形态的影响,也表明了SW处理后细胞的凋亡下降,并且在凋亡细胞减少同时细胞内的活性氧产生也明显减少。
4、与单纯缺血／缺氧组相比,0.09、0.12mJ/mm2能量SW处理组的H9c2细胞Bax蛋白表达下降,0.12mJ/mm2能量SW处理组的H9c2细胞Cleaved-Caspase-3蛋白表达降低,0.06、0.09、0.12mJ/mm2能量SW处理组的H9c2细胞Bcl-2蛋白表达升高。
5、与单纯缺血缺氧组相比,0.06、0.09、0.12mJ/mm2能量SW处理组的H9c2细胞磷酸化AKT蛋白表达升高,并有显著统计学差异(P值均<0.05)。结果提示PI3K-AKT通路可能参与了对SW减轻心肌细胞凋亡的调控。而0.06、0.09、0.12mJ/mm2能量SW处理组的H9c2细胞磷酸化ERK、p38MAPK蛋白与单纯缺血缺氧组比较表达无明显变化,结果提示经过SW处理后,ERK及p38MAPK通路并没有参与SW减轻心肌细胞凋亡的调控。
结论：
1、缺血缺氧可诱导H9c2细胞发生凋亡,促进细胞内的活性氧产生增多。
2、SW可减轻缺血缺氧诱导的心肌细胞的凋亡,降低凋亡相关蛋白Bax及Cleaved-Caspase-3的表达,升高抗凋亡蛋白Bcl-2的表达,并可减少细胞内活性氧的产生,抑制细胞凋亡。
3、PI3K-AKT通路可能参与SW对心肌细胞上述凋亡及抗凋亡蛋白表达的调控作用。
Objective
Apoptosis plays a key role in the pathogenesis in CAD due to loss of myocardial cell. The cell death program is activated in myocardial cell by various apoptotic stimuli including hypoxia, cytokines, increased oxidative stress and DNA damage. Several studies have reported that the apoptosis induced by ischemia/hypoxia is mainly dependent on the activation of mitochondrial pathways in cells. Many studies have demonstrated that inhibition of apoptosis can prevent the development of heart failure and improve heart function. Cardiac Shock Wave Therapy (CSWT) is currently the most advanced technology developed in recent years. CSWT could induced angiogenesis through up-regulation of VEGF and eNOS in ischemia myocardium and ameliorated myocardial ischemia and dysfunction in a porcine model of chronic myocardial ischemia, increase myocardial perfusion and improve the patient' s symptoms of angina and heart function. Does CSWT have any beneficial effect on ischemia/hypoxia (I/H) induced myocardial cell apoptosis? It is not clear at the present time. Based on the promising results from animal and clinical studies, the H9c2cellline, which was undergone ischemia/hypoxia treatment, was used for test the effects of SW on apoptosis, and to explore the possible mechanism of SW in improving myocardial function. The purpose of the study is to provid a new method for the treatment of ischemic heart disease.
Methods
1、The H9c2cells were treated in the ischemia/hypoxia conditions for12、24、36、48h respectively. The cell viability was examined in H9c2cells that were treated in I/H conditions at different times by MTT method.
2、The apoptosis models induced by I/H was established. According to the result of threshold experiment, the cells incubated in I/H conditions for24h were used in the subsequent experiments.The proportion of apoptotic H9c2cells was measured using Hoechst33342staining and an Annexin V-FITC Apoptosis Detection kit according to the manufacturer's protocol. Intracellular ROS levels were quantified to determine the oxidative stress to the H9c2cells in response to I/H condition using flow cytometry. Meanwhile, the protein levels of Bax、Bcl-2and Cleaved-Caspase-3were explored by western blot analysis.
3^The H9c2cells were treated in hypoxic serum-starved conditions for24h, and then treated with or without SW (500shots,0.06,0.09,0.12mJ/mm2). The apoptotic cell rate was determined by flow cytometry assay, cell viability was examined by the MTT assay, nuclear fragmentation was detected by Hoechst33342staining, and the mitochondrial-mediated intrinsic pathway of apoptosis was assessed by the expression of Bax, Bcl-2protein and Caspase3activation.
Results
1、It was shown, when cells incubated in I/H conditions, a significant time dependent reduction in cell viability was present compared to the control by MTT assay. The H9c2cell viability was decreased by26%after incubate in I/H conditions for24h, which is a medium degree of cell injury. So the cells incubated in I/H conditions for24h were used in the subsequent experiments.
2、After incubate H9c2cells in I/H conditions for24h, apoptosis markedly increased by Hoechst staining and Flow cytometry assay, Moreover, we found that I/H incubation could elevat ROS generation in a time-dependent manner.Also it was seen that less full length caspase3and more cleaved caspase3displayed than control, meanwhile, I/H increases the expression of pro-apoptosis protein Bax and decreases the expression of anti-apoptosis protein Bcl-2compared to control. It suggested that it is appropriate to incubate in I/H conditions for24h to induce cell apoptosis.
3、To determine if H9c2myoblast cell apoptosis induced by I/H could be attenuated by shock wave therapy, the H9c2cells were treated with500shots of shock wave at three different energy levels respectively (0.06,0.09and0.12mJ/mm2). The cells were divided into four groups:normal control (NC) group, normal control+shock wave (NC+SW) group, ischemia/hypoxia (I/H) group, and ischemia/hypoxia+shock wave I/H+SW) group. The results demonstrated that the I/H-induced cell death was significantly reduced, and the cell viability was increased after SW. Compared to treat with I/H alone, cells viability was strongly enhanced after SW treatment, with a maximum effect noted at0.12mJ/mm2. Moreover, the apoptotic effect of chromatin condensation and fragmentation induced by I/H was further improved which was demonstrated by Hoechst33342nuclear staining and SW decreased I/H-induced H9c2cell apoptosis rate by Flow cytometry assay, meanwhile the ROS generation was decreased by SW。
4、Our date showed that the expression of bcl-2was significantly increased in SW treat group (0.06,0.09,0.12mJ/mm2) compared to I/H treated group, while the expression of Bcl-2was increased in the NC group treated with SW (0.12mJ/mm2). SW (0.09,0.12mJ/mm2) also decreases the expression of pro-apoptosis protein Bax compared to I/H group. Moreover, we detected the Cleaved Caspase3. SW (0.12mJ/mm2) could significant reduce the activation of Caspase3.
5. Compared with I/H group, SW (0.06,0.09,0.12mJ/mm2) increases phosphorylation of AKT, while there is no significant difference between NC and NC+SW groups on AKT ratio. We also determine whether the other MAPK signal pathway such as p38MAPK and ERK signaling pathways could mediate the protective effect of SW on I/H-induced myocardial cell apoptosis. We found that there were no significant differences of phosphorylation of p38MAPK and ERK between SW and I/H group. The results indicate that SW's anti-apoptotic effects are mediated through AKT-dependent signaling pathways.
Conclusions
1、Ischemia and hypoxia could induce H9c2cell apoptosis and increase the ROS generation.
2、SW significantly reduced the I/H-induced cell death and increased the cell viability, decrease the expression of pro-apoptotic protein of Bax、Cleaved-Caspase-3and increase the expression of anti-apoptotic protein of Bcl-2, meanwhile the ROS generation was decreased by SW.
3、SW increases the phosphorylation of AKT, which indicates the activation of PI3K-AKT pathway, it demonstrate that the PI3K-Akt pathway may be involved in the SW effects on cell apoptosis.
大量研究显示细胞凋亡在冠心病的病理生理过程中起着重要的作用。有证据表明,心肌缺血、缺氧、缺血再灌注损伤、氧化应激等因素均可引起心肌及内皮细胞凋亡。多种因素例如氧化应激、缺氧、缺乏生长因子、化学及物理毒性损伤等可通过线粒体及内质网途径的激活而启动细胞凋亡。多项研究报道抑制细胞凋亡可以阻断心衰的发展并改善心功能。体外心脏震波(Cardiac Shock Wave Therapy,CSWT)是目前国际上新近发展起来的前沿科技,可通过上调血管内皮生长因子(VEGF)增加内皮型一氧化氮合酶(eNOS)的活性等途径使缺血区域的毛细血管生成增加,改善该区域心肌灌注。CSWT是否能够减轻缺血缺氧诱导的细胞凋亡目前少有报道,根据国内外目前的研究现状,我们将通过大鼠心肌细胞系H9c2缺血缺氧模型,检测SW对心肌细胞凋亡的影响,并进一步探讨其可能的机制,为缺血性心脏病的治疗提供新的思路。
方法：
选用大鼠心肌细胞来源的细胞系H9c2为研究对象,建立缺血缺氧损伤模型,行不同剂量震波(SW)治疗,观察其对调亡的影响。
1、将H9c2细胞换用无血清培养基,放入含有5%氧气-90%N2-5%C02的三气培养箱中培养,分别缺氧培养12、24、36、48h,MTT方法检测不同时间缺血缺氧对H9c2细胞活力的影响。
2、根据预实验的结果,H9c2细胞缺血缺氧处理24h,建立细胞凋亡模型。分别用Hoechst染色方法及AnnexinV-FITC检测方法检测H9c2细胞凋亡情况,应用流式细胞仪检测H9c2细胞内活性氧产生情况,并检测细胞凋亡相关因子Bax、Bcl-2和Cleaved-Caspase-3的表达情况。
3、H9c2细胞缺血缺氧处理24h后,分别用0.06、0.09、0.12mJ/mm2能量的SW处理细胞,运用MTT方法检测不同能量的SW对H9c2细胞活力的影响。Hoechst染色方法及Annexin V-FITC检测方法检测细胞凋亡并用流式细胞仪检测活性氧产生情况。Western Blot方法检测细胞凋亡相关因子Bax、Bcl-2和Cleaved-Caspase-3及Akt、ERK、p38MAPK信号通路的表达情况。
结果：
1、与对照组相比,缺血缺氧可降低H9c2细胞的细胞活力,并呈现时间依赖性。当缺血缺氧作用时间为24h,细胞活力下降约26%,这是一个中等程度的损伤,不会影响后续的实验结果,因此我们选用缺血缺氧24h作为后续实验处理条件。
2、将H9c2细胞缺血缺氧处理24h后,可以观察到缺血缺氧可诱导H9c2细胞发生凋亡,并且随着时间的延长细胞内活性氧的产生不断增多,Bax、Cleaved-Caspase-3的表达升高而Bcl-2表达下降,证明选择缺血缺氧24h作为处理条件是合适的。
3、为探讨SW对缺血缺氧诱导的H9c2细胞凋亡的作用,分别采用0.06、0.09、0.12mJ/mm2能量的SW处理细胞,实验分为四组,包括正常对照组(NC组)、正常对照+震波组(NC+SW组)、单纯缺血／缺氧组(I/H组)、缺血缺氧+震波组(I/H+SW组)。结果表明,与单纯缺血／缺氧组进行比较,0.06、0.09、0.12mJ/mm2能量SW处理的细胞活力均有明显提高,并有显著的统计学差异,应用0.12mJ/mm2能量SW处理细胞效果最明显。采用流式细胞术检测细胞凋亡情况,结果表明SW可减轻缺血缺氧诱导的H9c2细胞的凋亡,用Hoechest染色方式观察了SW处理对细胞核形态的影响,也表明了SW处理后细胞的凋亡下降,并且在凋亡细胞减少同时细胞内的活性氧产生也明显减少。
4、与单纯缺血／缺氧组相比,0.09、0.12mJ/mm2能量SW处理组的H9c2细胞Bax蛋白表达下降,0.12mJ/mm2能量SW处理组的H9c2细胞Cleaved-Caspase-3蛋白表达降低,0.06、0.09、0.12mJ/mm2能量SW处理组的H9c2细胞Bcl-2蛋白表达升高。
5、与单纯缺血缺氧组相比,0.06、0.09、0.12mJ/mm2能量SW处理组的H9c2细胞磷酸化AKT蛋白表达升高,并有显著统计学差异(P值均<0.05)。结果提示PI3K-AKT通路可能参与了对SW减轻心肌细胞凋亡的调控。而0.06、0.09、0.12mJ/mm2能量SW处理组的H9c2细胞磷酸化ERK、p38MAPK蛋白与单纯缺血缺氧组比较表达无明显变化,结果提示经过SW处理后,ERK及p38MAPK通路并没有参与SW减轻心肌细胞凋亡的调控。
结论：
1、缺血缺氧可诱导H9c2细胞发生凋亡,促进细胞内的活性氧产生增多。
2、SW可减轻缺血缺氧诱导的心肌细胞的凋亡,降低凋亡相关蛋白Bax及Cleaved-Caspase-3的表达,升高抗凋亡蛋白Bcl-2的表达,并可减少细胞内活性氧的产生,抑制细胞凋亡。
3、PI3K-AKT通路可能参与SW对心肌细胞上述凋亡及抗凋亡蛋白表达的调控作用。
Objective
Apoptosis plays a key role in the pathogenesis in CAD due to loss of myocardial cell. The cell death program is activated in myocardial cell by various apoptotic stimuli including hypoxia, cytokines, increased oxidative stress and DNA damage. Several studies have reported that the apoptosis induced by ischemia/hypoxia is mainly dependent on the activation of mitochondrial pathways in cells. Many studies have demonstrated that inhibition of apoptosis can prevent the development of heart failure and improve heart function. Cardiac Shock Wave Therapy (CSWT) is currently the most advanced technology developed in recent years. CSWT could induced angiogenesis through up-regulation of VEGF and eNOS in ischemia myocardium and ameliorated myocardial ischemia and dysfunction in a porcine model of chronic myocardial ischemia, increase myocardial perfusion and improve the patient' s symptoms of angina and heart function. Does CSWT have any beneficial effect on ischemia/hypoxia (I/H) induced myocardial cell apoptosis? It is not clear at the present time. Based on the promising results from animal and clinical studies, the H9c2cellline, which was undergone ischemia/hypoxia treatment, was used for test the effects of SW on apoptosis, and to explore the possible mechanism of SW in improving myocardial function. The purpose of the study is to provid a new method for the treatment of ischemic heart disease.
Methods
1、The H9c2cells were treated in the ischemia/hypoxia conditions for12、24、36、48h respectively. The cell viability was examined in H9c2cells that were treated in I/H conditions at different times by MTT method.
2、The apoptosis models induced by I/H was established. According to the result of threshold experiment, the cells incubated in I/H conditions for24h were used in the subsequent experiments.The proportion of apoptotic H9c2cells was measured using Hoechst33342staining and an Annexin V-FITC Apoptosis Detection kit according to the manufacturer's protocol. Intracellular ROS levels were quantified to determine the oxidative stress to the H9c2cells in response to I/H condition using flow cytometry. Meanwhile, the protein levels of Bax、Bcl-2and Cleaved-Caspase-3were explored by western blot analysis.
3^The H9c2cells were treated in hypoxic serum-starved conditions for24h, and then treated with or without SW (500shots,0.06,0.09,0.12mJ/mm2). The apoptotic cell rate was determined by flow cytometry assay, cell viability was examined by the MTT assay, nuclear fragmentation was detected by Hoechst33342staining, and the mitochondrial-mediated intrinsic pathway of apoptosis was assessed by the expression of Bax, Bcl-2protein and Caspase3activation.
Results
1、It was shown, when cells incubated in I/H conditions, a significant time dependent reduction in cell viability was present compared to the control by MTT assay. The H9c2cell viability was decreased by26%after incubate in I/H conditions for24h, which is a medium degree of cell injury. So the cells incubated in I/H conditions for24h were used in the subsequent experiments.
2、After incubate H9c2cells in I/H conditions for24h, apoptosis markedly increased by Hoechst staining and Flow cytometry assay, Moreover, we found that I/H incubation could elevat ROS generation in a time-dependent manner.Also it was seen that less full length caspase3and more cleaved caspase3displayed than control, meanwhile, I/H increases the expression of pro-apoptosis protein Bax and decreases the expression of anti-apoptosis protein Bcl-2compared to control. It suggested that it is appropriate to incubate in I/H conditions for24h to induce cell apoptosis.
3、To determine if H9c2myoblast cell apoptosis induced by I/H could be attenuated by shock wave therapy, the H9c2cells were treated with500shots of shock wave at three different energy levels respectively (0.06,0.09and0.12mJ/mm2). The cells were divided into four groups:normal control (NC) group, normal control+shock wave (NC+SW) group, ischemia/hypoxia (I/H) group, and ischemia/hypoxia+shock wave I/H+SW) group. The results demonstrated that the I/H-induced cell death was significantly reduced, and the cell viability was increased after SW. Compared to treat with I/H alone, cells viability was strongly enhanced after SW treatment, with a maximum effect noted at0.12mJ/mm2. Moreover, the apoptotic effect of chromatin condensation and fragmentation induced by I/H was further improved which was demonstrated by Hoechst33342nuclear staining and SW decreased I/H-induced H9c2cell apoptosis rate by Flow cytometry assay, meanwhile the ROS generation was decreased by SW。
4、Our date showed that the expression of bcl-2was significantly increased in SW treat group (0.06,0.09,0.12mJ/mm2) compared to I/H treated group, while the expression of Bcl-2was increased in the NC group treated with SW (0.12mJ/mm2). SW (0.09,0.12mJ/mm2) also decreases the expression of pro-apoptosis protein Bax compared to I/H group. Moreover, we detected the Cleaved Caspase3. SW (0.12mJ/mm2) could significant reduce the activation of Caspase3.
5. Compared with I/H group, SW (0.06,0.09,0.12mJ/mm2) increases phosphorylation of AKT, while there is no significant difference between NC and NC+SW groups on AKT ratio. We also determine whether the other MAPK signal pathway such as p38MAPK and ERK signaling pathways could mediate the protective effect of SW on I/H-induced myocardial cell apoptosis. We found that there were no significant differences of phosphorylation of p38MAPK and ERK between SW and I/H group. The results indicate that SW's anti-apoptotic effects are mediated through AKT-dependent signaling pathways.
Conclusions
1、Ischemia and hypoxia could induce H9c2cell apoptosis and increase the ROS generation.
2、SW significantly reduced the I/H-induced cell death and increased the cell viability, decrease the expression of pro-apoptotic protein of Bax、Cleaved-Caspase-3and increase the expression of anti-apoptotic protein of Bcl-2, meanwhile the ROS generation was decreased by SW.
3、SW increases the phosphorylation of AKT, which indicates the activation of PI3K-AKT pathway, it demonstrate that the PI3K-Akt pathway may be involved in the SW effects on cell apoptosis.
引文
1. Olivetti G, Quaini F, Sala R, Lagrasta C, Corradi D, Bonacina E, et al. Acute myocardial infarction in humans is associated with activation of programmed myocyte cell death in the surviving portion of the heart. Journal of molecular and cellular cardiology.1996;28(9):2005-16.
2. Saraste A, Pulkki K, Kallajoki M, Henriksen K, Parvinen M, Voipio-Pulkki L-M. Apoptosis in human acute myocardial infarction. Circulation.1997;95(2):320-3.
3. Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, et al. Apoptosis in myocytes in end-stage heart failure. New England Journal of Medicine. 1996;335(16):1182-9.
4. Guerra S, Leri A, Wang X, Finato N, Di Loreto C, Beltrami CA, et al. Myocyte death in the failing human heart is gender dependent. Circulation Research. 1999;85(9):856-66.
5. Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM, et al. A mechanistic role for cardiac myocyte apoptosis in heart failure. Journal of Clinical Investigation.2003;111(10):1497-504.
6. Aharinejad S, Andrukhova O, Lucas T, Zuckermann A, Wieselthaler G, Wolner E, et al. Programmed cell death in idiopathic dilated cardiomyopathy is mediated by suppression of the apoptosis inhibitor Apollon. The Annals of thoracic surgery. 2008;86(1):109-14.
7. Kubota T, McTiernan CF, Frye CS, Slawson SE, Lemster BH, Koretsky AP, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-a. Circulation Research.1997;81(4):627-35.
8. Bryant D, Becker L, Richardson J, Shelton J, Franco F, Peshock R, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-a. Circulation.1998;97(14):1375-81.
9. Lee Y, Gustafsson AB. Role of apoptosis in cardiovascular disease. Apoptosis. 2009;14(4):536-48.
10. Griendling KK, Sorescu D, Ushio-Fukai M. NAD (P) H oxidase role in cardiovascular biology and disease. Circulation Research.2000;86(5):494-501.
11. Konstantinidis K, Whelan RS, Kitsis RN. Mechanisms of cell death in heart disease. Arteriosclerosis, thrombosis, and vascular biology.2012;32(7):1552-62.
12. Gill C, Mestril R, Samali A. Losing heart:the role of apoptosis in heart disease—a novel therapeutic target? The FASEB journal.2002; 16(2):135-46.
13. Kockx MM, Knaapen MW. The role of apoptosis in vascular disease. The Journal of pathology.2000;190(3):267-80.
14. Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY).2012;4(5):330-49.
15. Jessup M, Brozena S. Heart failure N Engl J Med.2003;348:2007-18.
16. Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, et al. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation.2004;110(19):3055-61.
17. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy. Tohoku journal of experimental medicine. 2009;219(1).
18. Fukumoto Y, Ito A, Uwatoku T, Matoba T, Kishi T, Tanaka H, et al. Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease. Coronary artery disease.2006;17(1):63-70.
19. Kikuchi Y, Ito K, Ito Y, Shiroto T, Tsuburaya R, Aizawa K, et al. Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina pectoris. Circ J.2010;74(3):589-91.
20. Schmid JP, Capoferri M, Wahl A, Eshtehardi P, Hess OM. Cardiac Shock Wave Therapy for Chronic Refractory Angina Pectoris. A Prospective Placebo-Controlled Randomized Trial. Cardiovascular Therapeutics.2013;31(3):el-e6.
21. Wang Y, Guo T, Cai HY, Ma TK, Tao SM, Sun S, et al. Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease. Clinical cardiology.2010;33(11):693-9.
22. Yang P, Guo T, Wang W, Peng Y-Z, Wang Y, Zhou P, et al. Randomized and double-blind controlled clinical trial of extracorporeal cardiac shock wave therapy for coronary heart disease. Heart and Vessels.2013;28(3):284-91.
23. Vasyuk YA, Hadzegova AB, Shkolnik EL, Kopeleva MY, Krikunova OV, Iouchtchouk EN, et al. Initial clinical experience with extracorporeal shock wave therapy in treatment of ischemic heart failure. Congestive Heart Failure. 2010;16(5):226-30.
24. Gutersohn A, Caspari G. Shock waves upregulate vascular endothelial growth factor m-RNA in human umbilical vascular endothelial cells. Circulation. 2000;102(supplement 1):1-18.
25. G.Gotte, E.Amelio, S.Russo, et al. Short-time non-enzymmatic nitric oxide synthesis from L-arginine and hydrogen peroxide induced by shock waves treatment. FEBS Letters.2002;520:153-155.
26. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells:a new modality of increase efficacy of cell therapy in chronic hind limb Isehemia. Circulation.2006;114:2823-2830.
27. Nurzynska D, Meglio FD, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol.2008;34:334-342.
28. Fu M, Sun CK, Lin YC, et al. Extracorporeal shock wave therapy reverses isehemia—related left ventficular dysfunction and remodeling:molecular-cellular and funotional assessment. PLoS One.2011;6:e24342.
29. Kerr JF, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics. British journal of cancer. 1972;26(4):239.
30. Searle J, Lawson T, Abbott P, Harmon B, Kerr J. An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. The Journal of pathology. 1975;116(3):129-38.
31. Chen T-G, Chen T-L, Chang H-C, Tai Y-T, Cherng Y-G, Chang Y-T, et al. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway. Toxicology and applied pharmacology.2007;219(1):42-53.
32. Ferrari R, Ceconi C, Campo G, Cangiano E, Cavazza C, Secchiero P, et al. Mechanisms of remodelling:a question of life (stem cell production) and death (myocyte apoptosis). Circulation journal:official journal of the Japanese Circulation Society.2009;73(11):1973-82.
33. Danial NN, Korsmeyer SJ. Cell death:critical control points. Cell. 2004;116(2):205-19.
34. Tanaka M, Ito H, Adachi S, Akimoto H, Nishikawa T, Kasajima T, et al. Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circulation Research.1994;75(3):426-33.
35. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, et al. Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Laboratory investigation; a journal of technical methods and pathology.1996;74(1):86-107.
36. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, et al. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. Journal of Clinical Investigation.1998;101(7):1326.
37. Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA, et al. A Distinct Pathway Remodels Mitochondrial Cristae and Mobilizes Cytochrome< i> c during Apoptosis. Developmental cell.2002;2(1):55-67.
38. Tatsumi T, Shiraishi J, Keira N, Akashi K, Mano A, Yamanaka S, et al. Intracellular ATP is required for mitochondrial apoptotic pathways in isolated hypoxic rat cardiac myocytes. Cardiovascular research.2003;59(2):428-40.
39. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria:a primary site for Bcl-2 regulation of apoptosis. Science. 1997;275(5303):1132-6.
40. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, et al. Prevention of apoptosis by Bcl-2:release of cytochrome c from mitochondria blocked. Science. 1997;275(5303):1129-32.
41. Misao J, Hayakawa Y, Ohno M, Kato S, Fujiwara T, Fujiwara H. Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation. 1996;94(7):1506-12.
42. Nishikawa S, Tatsumi T, Shiraishi J, Matsunaga S, Takeda M, Mano A, et al. Nicorandil regulates Bcl-2 family proteins and protects cardiac myocytes against hypoxia-induced apoptosis. Journal of molecular and cellular cardiology. 2006;40(4):510-9.
43. Uwatoku T, Ito K, Abe K, Oi K, Hizume T, Sunagawa K, et al. Extracorporeal cardiac shock wave therapy improves left ventricular remodeling after acute myocardial infarction in pigs. Coronary artery disease.2007;18(5):397-404.
44. Solit DB, Basso AD, Olshen AB, Scher HI, Rosen N. Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol. Cancer research.2003;63(9):2139-44.
45. Mayo LD, Dormer DB. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proceedings of the National Academy of Sciences.2001;98(20):11598-603.
46. Fulton D, Gratton J-P, McCabe TJ, Fontana J, Fujio Y, Walsh K, et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 1999;399(6736):597-601.
47. Welch HC, Coadwell WJ, Stephens LR, Hawkins PT. Phosphoinositide 3-kinase-dependent activation of Rac. FEBS letters.2003;546(1):93-7.
48. Regula KM, Baetz D, Kirshenbaum LA. Nuclear factor-κB represses hypoxia-induced mitochondrial defects and cell death of ventricular myocytes. Circulation.2004;110(25):3795-802.
49. Hirai K, Hayashi T, Chan PH, Zeng J, Yang G-Y, Basus VJ, et al. PI3K inhibition in neonatal rat brain slices during and after hypoxia reduces phospho-Akt and increases cytosolic cytochrome< i> c and apoptosis. Molecular brain research. 2004;124(1):51-61.
50. Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung M-C. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nature cell biology. 2001;3(11):973-82.
51. Schmitt CA. Senescence, apoptosis and therapy—cutting the lifelines of cancer. Nature Reviews Cancer.2003;3(4):286-95.
52. Yao R, Cooper GM. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science.1995;267(5206):2003-6.
53. Gajewski TF, Thompson CB. Apoptosis meets signal transduction:elimination of a BAD influence. Cell.1996;87(4):589-92.
54. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 1997;278(5338):687-9.
55. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997;91(2):231-41.
56. Weiming X, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell research.2002;12(5):311-20.
57. Chauhan D, Pandey P, Ogata A, Teoh G, Krett N, Halgren R, et al. Cytochrome c-dependent and-independent induction of apoptosis in multiple myeloma cells. Journal of Biological Chemistry.1997;272(48):29995-7.
58. Tsimikas S, I Miller Y. Oxidative modification of lipoproteins:mechanisms, role in inflammation and potential clinical applications in cardiovascular disease. Current pharmaceutical design.2011;17(1):27-37.
59. Von Harsdorf R, Li P-F, Dietz R. Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation.1999;99(22):2934-41.
60. Leri A, Liu Y, Malhotra A, Li Q, Stiegler P, Claudio PP, et al. Pacing-induced heart failure in dogs enhances the expression of p53 and p53-dependent genes in ventricular myocytes. Circulation.1998;97(2):194-203.
61. Chandel NS, Schumacker PT, Arch RH. Reactive oxygen species are downstream products of TRAF-mediated signal transduction. Journal of Biological Chemistry. 2001;276(46):42728-36.
62. Jargin SV. Shock wave therapy of ischemic heart disease in the light of general pathology. International Journal of Cardiology.2010;144(1):116-7.
63. Jargin SV. Shock wave therapy of ischemic heart disease:some aspects of publication and advertizing in Russia. International Journal of Cardiology. 2010;145(2):241-2.
64. Di Meglio F, Nurzynska D, Castaldo C, Miraglia R, Romano V, De Angelis A, Piegari E, Russo S, Montagnani S:Cardiac shock wave therapy:assessment of safety and new insights into mechanisms of tissue regeneration. J Cell Mol Med 2012;16(4):936-942.
1. Wang Y,Guo T, Ma TK, et al. A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease. Cardiovasc Ultrasound,2012, 10:35.
2. Vasyuk YA, Hadzegova AB, Shkolnik EL, el al. Initial clinical experience with extracorporeal shock wave therapy in treatment of ischemic heart failure. Congest Heart Fail,2010,16:226-230.
3. Yang C, Wang Y, Pan JH, et al. A safety evaluation of extracorporeal cardiac shock wave therapy for refractory coronary heart disease. Chin J Cardiovasc Med.2010, 15:354-357. (in Chinese)
4. Wang Y, Guo T, Cai HY, et al. Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease. Chin J Cardiol.2010,38:711.715. (in Chinese)
5. Khattab AA, Brodersen B, Schuermann. Kuchenbrandt D, et al. Extracorporeal cardiac shock wave therapy:First experience in the everyday practice for treatment of chronic refractory angina peetoris. Int J Cardiol,2007,121:84-85.
6. Ito K, Fukumoto Y, Shimokawa H. Extmeorporeal shock wave therapy for ischemic cardiovascular disordePs. Am J Cardiovasc Drugs,2011,11:295-302,
7. Kikuehi Y, Ito K, Ito Y, et al. Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina peetoris. Circ J,2010,74:589-591.
8. Wang Y, Guo T, Cai HY, et al, Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease. Clin Cardiol,2010,33:693-699.
9. Yang P, Guo T, Wang W, et al. Randomized and double-blind controlled clinical trial of extraeorporeal cardiac shock wave therapy for coronary heart disease. Hcart Vessels,2012 Mar 30. [Epub ahead of print]
10. Sehmid JP, Capoferri M, Wahl A, et al. Cardiac shock wave therapy for chronic refractory angina pectoris. A prospective placebo-controlled randomised trial. Cardiovase Ther, 2012 Mar 23.[Epub ahead of print]
11. Kazmi WH, Rasheed SZ, Ahmed S, et al. Noninvasive therapy for the management of patients with advanced coronary artery disease. Coron Artery Dis,2012,23: 549-554.
12. Oi K. Fukurnoto Y, Ito K. et al. Extraeorporeal shock wave therapy ameliorates hindlirab ischemia in rabbits. Tohoku J Exp Med,2008.214:151-158.
13. Fukumoto Y, Ito A, Uwatoka T, et al. Extracorporeal cardiac shock wave therapy ameliorates myocardial isehemia in patients with severe coronary artery disease. Coron Artery Dis,2006.17:63-70.
14. Uwatoku T. Ito Kenta, Abe K, el al. Extracorpareal cardiac shock wave therapy improves left ventncular remodeling after acute myocardial infarction in pigs. Coron Artery Dis,2007,18:397-404.
15. Ito Y, Ito K, Shiroto T, et al. Cardiac shock wave therapy ameliorates left ventfieular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo, Coron Artery Dis,2010,21:304-311.
16. Fu M, Sun CK, Lin YC, et al. Extracorporeal shock wave therapy reverses isehemia—related left ventficular dysfunction and remodeling:molecular-cellular and funotional assessment. PLoS One.2011;6:e24342.
17. Mariotto S, de Prati AC, CavaJieri E, et al. Extraeorporeal shock wave therapy in inflammatory diseases:molecular mechanism that triggers anti-inflammatory action. Curt Med Chem.2009(16):2366-2372.
18. Wang Y, Guo T, Gu Y. Status and prospects of extracorporeal shock wave therapy in coronary heart disease. Chin J Cardiovasc Med,2010.15:318-320.(in Chinese)
19. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells:a new modality of increase efficacy of cell therapy in chronic hind limb Isehemia. Circulation.2006;114:2823-2830.
20. Nurzynska D, Meglio FD, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol.2008;34:334-342.
1. Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Yung S, et al. VEGF-induced adult neovascularization:recruitment, retention, and role of accessory cells. Cell.2006;124(1):175-89.
2. Manni L, Fausto VD, Fiore M, Aloe L. Repeated restraint and nerve growth factor administration in male and female mice:effect on sympathetic and cardiovascular mediators of the stress response. Current neurovascular research.2008;5(1):1-12.
3. Gale NW, Yancopoulos GD. Growth factors acting via endothelial cell-specific receptor tyrosine kinases:VEGFs, angiopoietins, and ephrins in vascular development. Genes & development.1999;13(9):1055-66.
4. Mariotto S, Cavalieri E, Amelio E, Ciampa AR, de Prati AC, Marlinghaus E, et al. Extracorporeal shock waves:from lithotripsy to anti-inflammatory action by NO production. Nitric Oxide.2005;12(2):89-96
5. Gutersohn A, Caspari G. Shock waves upregulate vascular endothelial growth factor m-RNA in human umbilical vascular endothelial cells. Circulation. 2000;102(supplement 1):1-18.
6. Uwatoku T, Ito K, Abe K, Oi K, Hizume T, Sunagawa K, et al. Extracorporeal cardiac shock wave therapy improves left ventricular remodeling after acute myocardial infarction in pigs. Coronary artery disease.2007;18(5):397-404.
7. Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, et al. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation.2004;110(19):3055-61.
8. Ito Y, Ito K, Shiroto T, Tsuburaya R, Yi GJ, Takeda M, et al. Cardiac shock wave therapy ameliorates left ventricular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo. Coronary artery disease. 2010;21(5):304-11.
9. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy. The Tohoku journal of experimental medicine. 2009;219(1):1-9
10. G.Gotte, E.Amelio, S.Russo, et al. Short-time non-enzymmatic nitric oxide synthesis from L-arginine and hydrogen peroxide induced by shock waves treatment. FEBS Letters.2002;520:153-155.
11. Mariotto S, de Prati AC, CavaJieri E, et al. Extraeorporeal shock wave therapy in inflammatory diseases:molecular mechanism that triggers anti-inflammatory action. Curt Med Chem.2009(16):2366-2372.
12. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells:a new modality of increase efficacy of cell therapy in chronic hind limb Isehemia. Circulation.2006;114:2823-2830.
13. Nurzynska D, Meglio FD, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol.2008;34:334-342.
14. Fu M, Sun CK, Lin YC, et al. Extracorporeal shock wave therapy reverses isehemia—related left ventficular dysfunction and remodeling:molecular-cellular and funotional assessment. PLoS One.2011;6:e24342.
15.蔡红雁,王钰,李琳等。体外心脏震波冠状动脉粥样硬化性心脏病患者血循环中内皮祖细胞及血管内皮生长因子的变化。中国组织工程研究与临床康复。2010.14(36)：6755-6758.
16. Saraste A, Pulkki K, Kallajoki M, Henriksen K, Parvinen M, Voipio-Pulkki L-M. Apoptosis in human acute myocardial infarction. Circulation.1997;95(2):320-3.
17. Aharinejad S, Andrukhova O, Lucas T, Zuckermann A, Wieselthaler G, Wolner E, et al. Programmed cell death in idiopathic dilated cardiomyopathy is mediated by suppression of the apoptosis inhibitor Apollon. The Annals of thoracic surgery. 2008;86(1):109-14.
18. Kubota T, McTiernan CF, Frye CS, Slawson SE, Lemster BH, Koretsky AP, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-a. Circulation Research.1997;81(4):627-35.
19. Bryant D, Becker L, Richardson J, Shelton J, Franco F, Peshock R, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-a. Circulation.1998;97(14):1375-81.
20. Gustafsson AB, Gottlieb RA. Recycle or die:the role of autophagy in cardioprotection. Journal of molecular and cellular cardiology.2008;44(4):654-61.
21. Yan L, Sadoshima J, Vatner DE, Vatner SF. Autophagy:a novel protective mechanism in chronic ischemia. Cell Cycle.2006;5(11):1175-7.
2. Saraste A, Pulkki K, Kallajoki M, Henriksen K, Parvinen M, Voipio-Pulkki L-M. Apoptosis in human acute myocardial infarction. Circulation.1997;95(2):320-3.
3. Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ, et al. Apoptosis in myocytes in end-stage heart failure. New England Journal of Medicine. 1996;335(16):1182-9.
4. Guerra S, Leri A, Wang X, Finato N, Di Loreto C, Beltrami CA, et al. Myocyte death in the failing human heart is gender dependent. Circulation Research. 1999;85(9):856-66.
5. Wencker D, Chandra M, Nguyen K, Miao W, Garantziotis S, Factor SM, et al. A mechanistic role for cardiac myocyte apoptosis in heart failure. Journal of Clinical Investigation.2003;111(10):1497-504.
6. Aharinejad S, Andrukhova O, Lucas T, Zuckermann A, Wieselthaler G, Wolner E, et al. Programmed cell death in idiopathic dilated cardiomyopathy is mediated by suppression of the apoptosis inhibitor Apollon. The Annals of thoracic surgery. 2008;86(1):109-14.
7. Kubota T, McTiernan CF, Frye CS, Slawson SE, Lemster BH, Koretsky AP, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-a. Circulation Research.1997;81(4):627-35.
8. Bryant D, Becker L, Richardson J, Shelton J, Franco F, Peshock R, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-a. Circulation.1998;97(14):1375-81.
9. Lee Y, Gustafsson AB. Role of apoptosis in cardiovascular disease. Apoptosis. 2009;14(4):536-48.
10. Griendling KK, Sorescu D, Ushio-Fukai M. NAD (P) H oxidase role in cardiovascular biology and disease. Circulation Research.2000;86(5):494-501.
11. Konstantinidis K, Whelan RS, Kitsis RN. Mechanisms of cell death in heart disease. Arteriosclerosis, thrombosis, and vascular biology.2012;32(7):1552-62.
12. Gill C, Mestril R, Samali A. Losing heart:the role of apoptosis in heart disease—a novel therapeutic target? The FASEB journal.2002; 16(2):135-46.
13. Kockx MM, Knaapen MW. The role of apoptosis in vascular disease. The Journal of pathology.2000;190(3):267-80.
14. Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of apoptosis in disease. Aging (Albany NY).2012;4(5):330-49.
15. Jessup M, Brozena S. Heart failure N Engl J Med.2003;348:2007-18.
16. Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, et al. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation.2004;110(19):3055-61.
17. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy. Tohoku journal of experimental medicine. 2009;219(1).
18. Fukumoto Y, Ito A, Uwatoku T, Matoba T, Kishi T, Tanaka H, et al. Extracorporeal cardiac shock wave therapy ameliorates myocardial ischemia in patients with severe coronary artery disease. Coronary artery disease.2006;17(1):63-70.
19. Kikuchi Y, Ito K, Ito Y, Shiroto T, Tsuburaya R, Aizawa K, et al. Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina pectoris. Circ J.2010;74(3):589-91.
20. Schmid JP, Capoferri M, Wahl A, Eshtehardi P, Hess OM. Cardiac Shock Wave Therapy for Chronic Refractory Angina Pectoris. A Prospective Placebo-Controlled Randomized Trial. Cardiovascular Therapeutics.2013;31(3):el-e6.
21. Wang Y, Guo T, Cai HY, Ma TK, Tao SM, Sun S, et al. Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease. Clinical cardiology.2010;33(11):693-9.
22. Yang P, Guo T, Wang W, Peng Y-Z, Wang Y, Zhou P, et al. Randomized and double-blind controlled clinical trial of extracorporeal cardiac shock wave therapy for coronary heart disease. Heart and Vessels.2013;28(3):284-91.
23. Vasyuk YA, Hadzegova AB, Shkolnik EL, Kopeleva MY, Krikunova OV, Iouchtchouk EN, et al. Initial clinical experience with extracorporeal shock wave therapy in treatment of ischemic heart failure. Congestive Heart Failure. 2010;16(5):226-30.
24. Gutersohn A, Caspari G. Shock waves upregulate vascular endothelial growth factor m-RNA in human umbilical vascular endothelial cells. Circulation. 2000;102(supplement 1):1-18.
25. G.Gotte, E.Amelio, S.Russo, et al. Short-time non-enzymmatic nitric oxide synthesis from L-arginine and hydrogen peroxide induced by shock waves treatment. FEBS Letters.2002;520:153-155.
26. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells:a new modality of increase efficacy of cell therapy in chronic hind limb Isehemia. Circulation.2006;114:2823-2830.
27. Nurzynska D, Meglio FD, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol.2008;34:334-342.
28. Fu M, Sun CK, Lin YC, et al. Extracorporeal shock wave therapy reverses isehemia—related left ventficular dysfunction and remodeling:molecular-cellular and funotional assessment. PLoS One.2011;6:e24342.
29. Kerr JF, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics. British journal of cancer. 1972;26(4):239.
30. Searle J, Lawson T, Abbott P, Harmon B, Kerr J. An electron-microscope study of the mode of cell death induced by cancer-chemotherapeutic agents in populations of proliferating normal and neoplastic cells. The Journal of pathology. 1975;116(3):129-38.
31. Chen T-G, Chen T-L, Chang H-C, Tai Y-T, Cherng Y-G, Chang Y-T, et al. Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway. Toxicology and applied pharmacology.2007;219(1):42-53.
32. Ferrari R, Ceconi C, Campo G, Cangiano E, Cavazza C, Secchiero P, et al. Mechanisms of remodelling:a question of life (stem cell production) and death (myocyte apoptosis). Circulation journal:official journal of the Japanese Circulation Society.2009;73(11):1973-82.
33. Danial NN, Korsmeyer SJ. Cell death:critical control points. Cell. 2004;116(2):205-19.
34. Tanaka M, Ito H, Adachi S, Akimoto H, Nishikawa T, Kasajima T, et al. Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circulation Research.1994;75(3):426-33.
35. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, et al. Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Laboratory investigation; a journal of technical methods and pathology.1996;74(1):86-107.
36. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, et al. Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. Journal of Clinical Investigation.1998;101(7):1326.
37. Scorrano L, Ashiya M, Buttle K, Weiler S, Oakes SA, Mannella CA, et al. A Distinct Pathway Remodels Mitochondrial Cristae and Mobilizes Cytochrome< i> c during Apoptosis. Developmental cell.2002;2(1):55-67.
38. Tatsumi T, Shiraishi J, Keira N, Akashi K, Mano A, Yamanaka S, et al. Intracellular ATP is required for mitochondrial apoptotic pathways in isolated hypoxic rat cardiac myocytes. Cardiovascular research.2003;59(2):428-40.
39. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria:a primary site for Bcl-2 regulation of apoptosis. Science. 1997;275(5303):1132-6.
40. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, et al. Prevention of apoptosis by Bcl-2:release of cytochrome c from mitochondria blocked. Science. 1997;275(5303):1129-32.
41. Misao J, Hayakawa Y, Ohno M, Kato S, Fujiwara T, Fujiwara H. Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation. 1996;94(7):1506-12.
42. Nishikawa S, Tatsumi T, Shiraishi J, Matsunaga S, Takeda M, Mano A, et al. Nicorandil regulates Bcl-2 family proteins and protects cardiac myocytes against hypoxia-induced apoptosis. Journal of molecular and cellular cardiology. 2006;40(4):510-9.
43. Uwatoku T, Ito K, Abe K, Oi K, Hizume T, Sunagawa K, et al. Extracorporeal cardiac shock wave therapy improves left ventricular remodeling after acute myocardial infarction in pigs. Coronary artery disease.2007;18(5):397-404.
44. Solit DB, Basso AD, Olshen AB, Scher HI, Rosen N. Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to Taxol. Cancer research.2003;63(9):2139-44.
45. Mayo LD, Dormer DB. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proceedings of the National Academy of Sciences.2001;98(20):11598-603.
46. Fulton D, Gratton J-P, McCabe TJ, Fontana J, Fujio Y, Walsh K, et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 1999;399(6736):597-601.
47. Welch HC, Coadwell WJ, Stephens LR, Hawkins PT. Phosphoinositide 3-kinase-dependent activation of Rac. FEBS letters.2003;546(1):93-7.
48. Regula KM, Baetz D, Kirshenbaum LA. Nuclear factor-κB represses hypoxia-induced mitochondrial defects and cell death of ventricular myocytes. Circulation.2004;110(25):3795-802.
49. Hirai K, Hayashi T, Chan PH, Zeng J, Yang G-Y, Basus VJ, et al. PI3K inhibition in neonatal rat brain slices during and after hypoxia reduces phospho-Akt and increases cytosolic cytochrome< i> c and apoptosis. Molecular brain research. 2004;124(1):51-61.
50. Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung M-C. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nature cell biology. 2001;3(11):973-82.
51. Schmitt CA. Senescence, apoptosis and therapy—cutting the lifelines of cancer. Nature Reviews Cancer.2003;3(4):286-95.
52. Yao R, Cooper GM. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science.1995;267(5206):2003-6.
53. Gajewski TF, Thompson CB. Apoptosis meets signal transduction:elimination of a BAD influence. Cell.1996;87(4):589-92.
54. del Peso L, Gonzalez-Garcia M, Page C, Herrera R, Nunez G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science. 1997;278(5338):687-9.
55. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997;91(2):231-41.
56. Weiming X, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell research.2002;12(5):311-20.
57. Chauhan D, Pandey P, Ogata A, Teoh G, Krett N, Halgren R, et al. Cytochrome c-dependent and-independent induction of apoptosis in multiple myeloma cells. Journal of Biological Chemistry.1997;272(48):29995-7.
58. Tsimikas S, I Miller Y. Oxidative modification of lipoproteins:mechanisms, role in inflammation and potential clinical applications in cardiovascular disease. Current pharmaceutical design.2011;17(1):27-37.
59. Von Harsdorf R, Li P-F, Dietz R. Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation.1999;99(22):2934-41.
60. Leri A, Liu Y, Malhotra A, Li Q, Stiegler P, Claudio PP, et al. Pacing-induced heart failure in dogs enhances the expression of p53 and p53-dependent genes in ventricular myocytes. Circulation.1998;97(2):194-203.
61. Chandel NS, Schumacker PT, Arch RH. Reactive oxygen species are downstream products of TRAF-mediated signal transduction. Journal of Biological Chemistry. 2001;276(46):42728-36.
62. Jargin SV. Shock wave therapy of ischemic heart disease in the light of general pathology. International Journal of Cardiology.2010;144(1):116-7.
63. Jargin SV. Shock wave therapy of ischemic heart disease:some aspects of publication and advertizing in Russia. International Journal of Cardiology. 2010;145(2):241-2.
64. Di Meglio F, Nurzynska D, Castaldo C, Miraglia R, Romano V, De Angelis A, Piegari E, Russo S, Montagnani S:Cardiac shock wave therapy:assessment of safety and new insights into mechanisms of tissue regeneration. J Cell Mol Med 2012;16(4):936-942.
1. Wang Y,Guo T, Ma TK, et al. A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease. Cardiovasc Ultrasound,2012, 10:35.
2. Vasyuk YA, Hadzegova AB, Shkolnik EL, el al. Initial clinical experience with extracorporeal shock wave therapy in treatment of ischemic heart failure. Congest Heart Fail,2010,16:226-230.
3. Yang C, Wang Y, Pan JH, et al. A safety evaluation of extracorporeal cardiac shock wave therapy for refractory coronary heart disease. Chin J Cardiovasc Med.2010, 15:354-357. (in Chinese)
4. Wang Y, Guo T, Cai HY, et al. Extracorporeal cardiac shock wave therapy for treatment of coronary artery disease. Chin J Cardiol.2010,38:711.715. (in Chinese)
5. Khattab AA, Brodersen B, Schuermann. Kuchenbrandt D, et al. Extracorporeal cardiac shock wave therapy:First experience in the everyday practice for treatment of chronic refractory angina peetoris. Int J Cardiol,2007,121:84-85.
6. Ito K, Fukumoto Y, Shimokawa H. Extmeorporeal shock wave therapy for ischemic cardiovascular disordePs. Am J Cardiovasc Drugs,2011,11:295-302,
7. Kikuehi Y, Ito K, Ito Y, et al. Double-blind and placebo-controlled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina peetoris. Circ J,2010,74:589-591.
8. Wang Y, Guo T, Cai HY, et al, Cardiac shock wave therapy reduces angina and improves myocardial function in patients with refractory coronary artery disease. Clin Cardiol,2010,33:693-699.
9. Yang P, Guo T, Wang W, et al. Randomized and double-blind controlled clinical trial of extraeorporeal cardiac shock wave therapy for coronary heart disease. Hcart Vessels,2012 Mar 30. [Epub ahead of print]
10. Sehmid JP, Capoferri M, Wahl A, et al. Cardiac shock wave therapy for chronic refractory angina pectoris. A prospective placebo-controlled randomised trial. Cardiovase Ther, 2012 Mar 23.[Epub ahead of print]
11. Kazmi WH, Rasheed SZ, Ahmed S, et al. Noninvasive therapy for the management of patients with advanced coronary artery disease. Coron Artery Dis,2012,23: 549-554.
12. Oi K. Fukurnoto Y, Ito K. et al. Extraeorporeal shock wave therapy ameliorates hindlirab ischemia in rabbits. Tohoku J Exp Med,2008.214:151-158.
13. Fukumoto Y, Ito A, Uwatoka T, et al. Extracorporeal cardiac shock wave therapy ameliorates myocardial isehemia in patients with severe coronary artery disease. Coron Artery Dis,2006.17:63-70.
14. Uwatoku T. Ito Kenta, Abe K, el al. Extracorpareal cardiac shock wave therapy improves left ventncular remodeling after acute myocardial infarction in pigs. Coron Artery Dis,2007,18:397-404.
15. Ito Y, Ito K, Shiroto T, et al. Cardiac shock wave therapy ameliorates left ventfieular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo, Coron Artery Dis,2010,21:304-311.
16. Fu M, Sun CK, Lin YC, et al. Extracorporeal shock wave therapy reverses isehemia—related left ventficular dysfunction and remodeling:molecular-cellular and funotional assessment. PLoS One.2011;6:e24342.
17. Mariotto S, de Prati AC, CavaJieri E, et al. Extraeorporeal shock wave therapy in inflammatory diseases:molecular mechanism that triggers anti-inflammatory action. Curt Med Chem.2009(16):2366-2372.
18. Wang Y, Guo T, Gu Y. Status and prospects of extracorporeal shock wave therapy in coronary heart disease. Chin J Cardiovasc Med,2010.15:318-320.(in Chinese)
19. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells:a new modality of increase efficacy of cell therapy in chronic hind limb Isehemia. Circulation.2006;114:2823-2830.
20. Nurzynska D, Meglio FD, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol.2008;34:334-342.
1. Grunewald M, Avraham I, Dor Y, Bachar-Lustig E, Itin A, Yung S, et al. VEGF-induced adult neovascularization:recruitment, retention, and role of accessory cells. Cell.2006;124(1):175-89.
2. Manni L, Fausto VD, Fiore M, Aloe L. Repeated restraint and nerve growth factor administration in male and female mice:effect on sympathetic and cardiovascular mediators of the stress response. Current neurovascular research.2008;5(1):1-12.
3. Gale NW, Yancopoulos GD. Growth factors acting via endothelial cell-specific receptor tyrosine kinases:VEGFs, angiopoietins, and ephrins in vascular development. Genes & development.1999;13(9):1055-66.
4. Mariotto S, Cavalieri E, Amelio E, Ciampa AR, de Prati AC, Marlinghaus E, et al. Extracorporeal shock waves:from lithotripsy to anti-inflammatory action by NO production. Nitric Oxide.2005;12(2):89-96
5. Gutersohn A, Caspari G. Shock waves upregulate vascular endothelial growth factor m-RNA in human umbilical vascular endothelial cells. Circulation. 2000;102(supplement 1):1-18.
6. Uwatoku T, Ito K, Abe K, Oi K, Hizume T, Sunagawa K, et al. Extracorporeal cardiac shock wave therapy improves left ventricular remodeling after acute myocardial infarction in pigs. Coronary artery disease.2007;18(5):397-404.
7. Nishida T, Shimokawa H, Oi K, Tatewaki H, Uwatoku T, Abe K, et al. Extracorporeal cardiac shock wave therapy markedly ameliorates ischemia-induced myocardial dysfunction in pigs in vivo. Circulation.2004;110(19):3055-61.
8. Ito Y, Ito K, Shiroto T, Tsuburaya R, Yi GJ, Takeda M, et al. Cardiac shock wave therapy ameliorates left ventricular remodeling after myocardial ischemia-reperfusion injury in pigs in vivo. Coronary artery disease. 2010;21(5):304-11.
9. Ito K, Fukumoto Y, Shimokawa H. Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy. The Tohoku journal of experimental medicine. 2009;219(1):1-9
10. G.Gotte, E.Amelio, S.Russo, et al. Short-time non-enzymmatic nitric oxide synthesis from L-arginine and hydrogen peroxide induced by shock waves treatment. FEBS Letters.2002;520:153-155.
11. Mariotto S, de Prati AC, CavaJieri E, et al. Extraeorporeal shock wave therapy in inflammatory diseases:molecular mechanism that triggers anti-inflammatory action. Curt Med Chem.2009(16):2366-2372.
12. Aicher A, Heeschen C, Sasaki K, et al. Low-energy shock wave for enhancing recruitment of endothelial progenitor cells:a new modality of increase efficacy of cell therapy in chronic hind limb Isehemia. Circulation.2006;114:2823-2830.
13. Nurzynska D, Meglio FD, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol.2008;34:334-342.
14. Fu M, Sun CK, Lin YC, et al. Extracorporeal shock wave therapy reverses isehemia—related left ventficular dysfunction and remodeling:molecular-cellular and funotional assessment. PLoS One.2011;6:e24342.
15.蔡红雁,王钰,李琳等。体外心脏震波冠状动脉粥样硬化性心脏病患者血循环中内皮祖细胞及血管内皮生长因子的变化。中国组织工程研究与临床康复。2010.14(36)：6755-6758.
16. Saraste A, Pulkki K, Kallajoki M, Henriksen K, Parvinen M, Voipio-Pulkki L-M. Apoptosis in human acute myocardial infarction. Circulation.1997;95(2):320-3.
17. Aharinejad S, Andrukhova O, Lucas T, Zuckermann A, Wieselthaler G, Wolner E, et al. Programmed cell death in idiopathic dilated cardiomyopathy is mediated by suppression of the apoptosis inhibitor Apollon. The Annals of thoracic surgery. 2008;86(1):109-14.
18. Kubota T, McTiernan CF, Frye CS, Slawson SE, Lemster BH, Koretsky AP, et al. Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-a. Circulation Research.1997;81(4):627-35.
19. Bryant D, Becker L, Richardson J, Shelton J, Franco F, Peshock R, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-a. Circulation.1998;97(14):1375-81.
20. Gustafsson AB, Gottlieb RA. Recycle or die:the role of autophagy in cardioprotection. Journal of molecular and cellular cardiology.2008;44(4):654-61.
21. Yan L, Sadoshima J, Vatner DE, Vatner SF. Autophagy:a novel protective mechanism in chronic ischemia. Cell Cycle.2006;5(11):1175-7.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |