血管过氧化物酶1介导高血压心肌重构及机制研究
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摘要
研究背景：心肌组织受容量或压力负荷、神经体液激素及细胞因子等各种因素诱导所致心肌重构,即心肌肥大和心肌炎性浸润及纤维化改变,不仅是心血管疾病发病率和病死率的独立危险因素,也是导致慢性心力衰竭的首要原因。近年来大量研究表明氧化应激在心肌重构中扮演了重要作用,上述多种因素可通过激活NADPH氧化酶(NOX)产生大量活性氧自由基(reactive oxygen species, ROS),其活性成分超氧阴离子(02-)和过氧化氢(H202)活化下游氧化还原及促炎相关信号传导通路,从而促使心肌细胞肥大、胶原纤维增加等病理生理过程的发展,最终引起心脏结构和功能改变。
血管过氧化物酶1(vascular peroxide1, VPO1)是新近发现的一种心血管系统中的过氧化物酶家族成员。作为NADPH氧化酶下游信号传导中一种酶,VPO1通过催化NOX来源的H202生成更强的氧化剂次氯酸(hypochlorous acid, HOCl),进一步放大氧化应激效应。我们新近研究证据显示NOX/VPO1信号通路介导的氧化应激在心肌缺血再灌注损伤,内皮细胞凋亡和平滑肌细胞增殖过程中有着重要作用。鉴于氧化应激在心肌重构中的重要作用,我们推测VPO1可能介导了高血压心肌重构,本研究首先在动物水平探讨VPO1与高血压心肌重构的相关性,在此基础上,从细胞水平进一步研究VPO1介导心肌重构及其相关机制。
第一部分VPO1介导高血压大鼠心肌重构
目的：探讨VPO1是否参与了自发性高血压大鼠心肌肥大及纤维化过程。
方法：20周龄雄性自发性高血压大鼠(spontaneously hypertensive rat)12只,即高血压组(SHR组,n=12),12只同龄雄性Wistar-Kyoto大鼠作为正常血压对照组(WKY组,n=12),测量尾动脉收缩压,并用超声心动仪检测心脏形态学及相关心功能指标。采用HE染色观察心肌组织病理变化,Masson染色观察心肌组织中胶原含量变化,免疫组织化学方法检测心肌组织中VPOl蛋白表达水平、Western blot (免疫印迹法)测定心肌组织中Nox2. Nox4和VPO1蛋白的表达水平,RT-PCR方法测定心肌组织中Nox2、Nox4、VPO1以及Ⅰ、Ⅲ型胶原mRNA的表达水平。
结果：与WKY正常血压组大鼠相比,SHR组大鼠血压显著升高,心室出现明显的向心性肥厚,心肌细胞体积增大和胶原纤维含量增加,心脏舒张功能明显降低；SHR组心肌组织中Nox2、Nox4和VPO1蛋白和mRNA的表达显著上调；SHR组心肌组织中的Ⅰ、Ⅲ型胶原纤维mRNA表达增加。
结论：
VPO1可能参与了高血压大鼠的心脏重构,其机制可能涉及NOX/VPO1信号通路。
第二部分VPO1介导AngⅡ诱导心肌细胞重构及相关机制
目的：探讨VPO1是否介导了Ang Ⅱ诱导心肌细胞重构及相关机制
方法：
(1)研究AngⅡ处理心肌细胞(H9c2)对VPO1表达水平的影响。量效实验分组：对照组和不同浓度的Ang Ⅱ组(用含10-7M,10-6M,10-5MAngⅡ的培养液孵育H9c2细胞24h)。时效实验分组：对照组和根据量效实验所确定的最佳Ang Ⅱ浓度处理不同时间组(12h,24h,48h)。采用Real-Time PCR及Western-blot法分别从基因及蛋白水平检钡(?)vpo1表达水平。
(2)研究NADPH氧化酶抑制剂二苯基碘(DPI)、过氧化氢水解酶(catalase)和VPO1抑制剂氨基苯甲酰肼(aminobenzoic acid hydrazide, ABAH)分别预处理对AngⅡ诱导H9c2细胞VPO1表达水平、心肌细胞肥大、纤维化以及相关途径影响。实验分组：空白对照组：用含1%小牛血清的高糖DMEM培养液孵育H9c2细胞24h; AngⅡ组：用含10-6MAngⅡ的培养液孵育H9c2细胞24h；+抑制剂组(三组)：分别用100μM DPI,300μM catalase,400μM ABAH预处理H9c2细胞2h后,加入终浓度为10-6M的AngⅡ培养液孵育H9c2细胞24h,采用Real-Time PCR及Western-blot法分别从基因及蛋白水平检测Nox2、Nox4、VPO1表达；心肌细胞肥大评价：结晶紫染色后拍照并用Image J软件分析心肌细胞表面积,采用Real-time PCR测定BNP、ANF mRNA水平；心肌细胞纤维化评价：采用Real-time PCR测定Ⅰ、Ⅲ型胶原纤维mRNA表达水平,并用天狼猩红染色测定纤维胶原含量；VPO1介导Ang Ⅱ诱导心肌重构相关机制研究：分别测定各组心肌细胞中MAPK (p-38、 p-ERK、p-JNK)蛋白表达水平。细胞内H2O2和HOCl水平分别通过酶联免疫法(ELISA)和3-氯酪氨酸蛋白免疫组化染色检测。
结果：
(1) Ang Ⅱ诱导心肌细胞VPO1水平表达增高呈浓度依赖性,并能被NADPH氧化酶抑制剂(DPI)及catalse抑制。
(2)与对照组相比,Ang Ⅱ(10-6M)处理H9c2细胞24h显著上调细胞Nox2, VPO1表达水平(P<0.01),并升高BNP、ANF、Ⅰ、Ⅲ型胶原纤维mRNA水平的表达(P<0.01),及纤维胶原含量。同时Ang Ⅱ能诱导H9c2细胞内H2O2和3-氯酪氨酸蛋白生成增加。NADPH氧化酶抑制剂DPI、catalase及VPO1抑制剂(ABAH)预处理可不同程度抑制Ang Ⅱ的上述作用。
(3) Ang Ⅱ诱导心肌细胞重构同时,能显著上调了MAPK (p-38、p-ERK、p-JNK)蛋白表达水平,DPI、catalase能不同程度抑制MAPK蛋白表达增加,但VPO1抑制剂仅能部分抑制Ang Ⅱ上调p-ERK蛋白表达。
结论：
VPO1至少部分介导了Ang Ⅱ诱导的心肌细胞重构,其机制可能涉及Nox2/H2O2/VPO1/HOC1/ERK1/2信号传导途径。
Background Cardiac remodeling in response to stress and injury, such as pressure or volume overload, neurohormones and cytokines, is characterized by cardiac hypertrophy and myocardial inflammation and fibrosis, which is a major risk factor for cardiovascular morbidity and mortality and a leading cause of chronic heart failure. A large body of evidence shows that oxidative stress plays an important role in the pathological process of cardiac remodeling. Stimulus mentioned above can activate the NADPH oxidases (NOX), a major resource of ROS, and result in large production of supreoxide (O2-) and peroxide (H2O2) with subsequent downstream of redox-sensitive signaling pathways, which is involved in the development of pathologic process of hypertrophy response and collagen deposition.
Vascμlar peroxidase1(VPO1) is a newly identified novel family member of peroxidases in cardiovascular system. VPO1as an enzyme that is downstream of NOX, functions to utilize NOX-derived hydrogen peroxide (H2O2) to produce a strong oxidant-hypochlorous acid (HOCl), and thus the oxidative stress is dramatically amplified. Several lines of evidence suggest that the NOX/VPO1pathway-mediated oxidative stress plays an important role in myocardial ischemia-reperfusion injury, endothelial cell apoptosis and smooth muscle cell proliferation. In addition, VPO1can be secreted into the extracellular space to participate in extracellular matrix formation, suggesting that VPO1may also play a role in cardiac remodeling, The present study was first to determine whether VPO1is implicated in hypertensive cardiac remodeling in vivo, and then to investigate whether VPO1is involved in Ang II induced cardiac remodeling in vitro and to explore the underlying mechanism.
Chapter I Relationship between VPO1and hypertensive cardiac remodeling
Objectives:To investigate the relationship between VPO1and hypertensive cardiac remodeling.
Methods:Twelve male spontaneously hypertensive rats (20-week-old) were served as hypertension group (SHR group), and Twelve male Wistar-Kyoto rats with the same age served as the normotensive control group (WKY group). Blood pressure was measured and after performing echocardiography analysis, the heart was isolated. Pathological changes of myocardial tissue was measured by HE staining, myocardial collagen deposition was measured by Masson staining, and the expression of VPO1was detected by immunohistochemistry。The expression of Nox2, Nox4and VPO1was also determined by western blot and the mRNA expression of type I Ⅲ collagen, Nox2、Nox4and VPO1was measured by real time-PCR.
Results:Compared with WKY group, blood pressure, thickness of ventricle, collagen deposition, mRNA and protein expression of Nox2、Nox4and VPO1, mRNA expression of type Ⅰ、Ⅲ collagen were all significantly increased in SHR group, whereas cardiac diastolic function is impaired in SHR group.
Conclusion:The present reserch indicates that VPO1may be involved in the process of Hypertensive rats cardiac remodeling via NOX/VP01-signaling pathways.
Chapter Ⅱ VPO1mediates Ang Ⅱ-induced myocardial remodeling in H9c2cells
Objective:To investigate whether VPO1mediates Ang Ⅱ-induced cardiac remodeling in H9c2cells and to explore the underlying mechanism.
Methods:(1) The effect of Ang Ⅱ on the VPO1expression in H9c2cells was observed. H9c2cells were treated with different concentrations of Ang Ⅱ (10-7M,10-6M,10-5M Ang Ⅱ) for24h, and H9c2cell were treated with Ang II for different time (12h,24h,48h). The expressions of VPO1were determined by Western-Blot and Real-Time PCR.(2) To study the effect of NADPH inhibitor diphenyleneio-donium (DPI), catalase, VPO1inhibitor-ABAH on Ang Ⅱ induced cardiac remodeling. Cultured H9c2cells were randomly divided into five groups:control group:cells were incubated in high glucose DMEM containing1%fetal bovine serum for24hours; Ang Ⅱ treatment group:cells were incubated in high glucose DMEM containing10-6M Ang II for24hours; Ang Ⅱ+DPI group:cells were pretreated with100μM DPI (NADPH oxidase inhibitor) for2hours prior to Ang II exposure; Ang Ⅱ+Catalase group: cells were pretreated with300μM Catalase for2hours prior to Ang II exposure; Ang II+ABAH group:cells were pretreated with400μM ABAH for2hours prior to Ang Ⅱ exposure; The mRNA and proteins expression of Nox2、Nox4and VPO1were determined by western blot and real time-PCR. Hypertrophy assay:H9c2cell were stained with crystal violet and the cellular size were calculated by Image software. Gene expression of BNP、ANF was tested by RT-PCR. Fibrosis assay: collagen type Ⅰ、Ⅲ gene expression was measured by RT-PCR, and collagen content was valued by Sirus Red staining. To explore the underlying mechanism:the protein expression of p-38、p-ERK and p-JNK were evaluated by western blot. The level of H2O2and HOC1were detected respectively through ELISA and3-chlorotyrosine protein immuno assay.
Results:
(1) In vitro, these results suggest that VPO1is unregulated by Ang II in a dose-depended manner, which can be abrogated both in gene and protein level by different inhibitors, such as NADPH inhibitors-DPI, catalase, and the VPO1inhibitors (aminobenzoic acid hydrazide, ABAH).
(2) Compared with the control group, Ang Ⅱ (10'6M) significantly increased the expression of Nox2, VPO1, the collagen content, the cellular size, and also up-regulated the gene expression of BNP, ANF, type In Ⅲ collagen. In addition, Ang II also increased the production of H2O2and the protein expression of3-chlorotyrosine protein. These effects of Ang II on H9c2cells were inhibited in a different degree by the pretreatment of DPI, catalase and the VPO1inhibitor (ABAH).
(3)Ang II induced myocardial remodeling, followed by up-regulating the MAPK (p-ERK, p-38, p-JNK) protein expression, which were attenuated by the NADPH oxidase inhibitor (DPI) and catalase. However, the VPOl inhibitor (ABAH) can only inhibit the up-regulation of p-ERK induced by Ang II.
Conclusion:
The present study has demonstrated that VPO1is at least part involved in the process of the Ang Ⅱ induced cardiac remodeling, both in myocardial hypertrophy and fibrosis. The results indicate that VPO1play a role via Nox2/H2O2/VPO1/HOCl/ERK1/2signaling pathway in the pathology of Ang Ⅱ induced cardiac remodeling.
血管过氧化物酶1(vascular peroxide1, VPO1)是新近发现的一种心血管系统中的过氧化物酶家族成员。作为NADPH氧化酶下游信号传导中一种酶,VPO1通过催化NOX来源的H202生成更强的氧化剂次氯酸(hypochlorous acid, HOCl),进一步放大氧化应激效应。我们新近研究证据显示NOX/VPO1信号通路介导的氧化应激在心肌缺血再灌注损伤,内皮细胞凋亡和平滑肌细胞增殖过程中有着重要作用。鉴于氧化应激在心肌重构中的重要作用,我们推测VPO1可能介导了高血压心肌重构,本研究首先在动物水平探讨VPO1与高血压心肌重构的相关性,在此基础上,从细胞水平进一步研究VPO1介导心肌重构及其相关机制。
第一部分VPO1介导高血压大鼠心肌重构
目的：探讨VPO1是否参与了自发性高血压大鼠心肌肥大及纤维化过程。
方法：20周龄雄性自发性高血压大鼠(spontaneously hypertensive rat)12只,即高血压组(SHR组,n=12),12只同龄雄性Wistar-Kyoto大鼠作为正常血压对照组(WKY组,n=12),测量尾动脉收缩压,并用超声心动仪检测心脏形态学及相关心功能指标。采用HE染色观察心肌组织病理变化,Masson染色观察心肌组织中胶原含量变化,免疫组织化学方法检测心肌组织中VPOl蛋白表达水平、Western blot (免疫印迹法)测定心肌组织中Nox2. Nox4和VPO1蛋白的表达水平,RT-PCR方法测定心肌组织中Nox2、Nox4、VPO1以及Ⅰ、Ⅲ型胶原mRNA的表达水平。
结果：与WKY正常血压组大鼠相比,SHR组大鼠血压显著升高,心室出现明显的向心性肥厚,心肌细胞体积增大和胶原纤维含量增加,心脏舒张功能明显降低；SHR组心肌组织中Nox2、Nox4和VPO1蛋白和mRNA的表达显著上调；SHR组心肌组织中的Ⅰ、Ⅲ型胶原纤维mRNA表达增加。
结论：
VPO1可能参与了高血压大鼠的心脏重构,其机制可能涉及NOX/VPO1信号通路。
第二部分VPO1介导AngⅡ诱导心肌细胞重构及相关机制
目的：探讨VPO1是否介导了Ang Ⅱ诱导心肌细胞重构及相关机制
方法：
(1)研究AngⅡ处理心肌细胞(H9c2)对VPO1表达水平的影响。量效实验分组：对照组和不同浓度的Ang Ⅱ组(用含10-7M,10-6M,10-5MAngⅡ的培养液孵育H9c2细胞24h)。时效实验分组：对照组和根据量效实验所确定的最佳Ang Ⅱ浓度处理不同时间组(12h,24h,48h)。采用Real-Time PCR及Western-blot法分别从基因及蛋白水平检钡(?)vpo1表达水平。
(2)研究NADPH氧化酶抑制剂二苯基碘(DPI)、过氧化氢水解酶(catalase)和VPO1抑制剂氨基苯甲酰肼(aminobenzoic acid hydrazide, ABAH)分别预处理对AngⅡ诱导H9c2细胞VPO1表达水平、心肌细胞肥大、纤维化以及相关途径影响。实验分组：空白对照组：用含1%小牛血清的高糖DMEM培养液孵育H9c2细胞24h; AngⅡ组：用含10-6MAngⅡ的培养液孵育H9c2细胞24h；+抑制剂组(三组)：分别用100μM DPI,300μM catalase,400μM ABAH预处理H9c2细胞2h后,加入终浓度为10-6M的AngⅡ培养液孵育H9c2细胞24h,采用Real-Time PCR及Western-blot法分别从基因及蛋白水平检测Nox2、Nox4、VPO1表达；心肌细胞肥大评价：结晶紫染色后拍照并用Image J软件分析心肌细胞表面积,采用Real-time PCR测定BNP、ANF mRNA水平；心肌细胞纤维化评价：采用Real-time PCR测定Ⅰ、Ⅲ型胶原纤维mRNA表达水平,并用天狼猩红染色测定纤维胶原含量；VPO1介导Ang Ⅱ诱导心肌重构相关机制研究：分别测定各组心肌细胞中MAPK (p-38、 p-ERK、p-JNK)蛋白表达水平。细胞内H2O2和HOCl水平分别通过酶联免疫法(ELISA)和3-氯酪氨酸蛋白免疫组化染色检测。
结果：
(1) Ang Ⅱ诱导心肌细胞VPO1水平表达增高呈浓度依赖性,并能被NADPH氧化酶抑制剂(DPI)及catalse抑制。
(2)与对照组相比,Ang Ⅱ(10-6M)处理H9c2细胞24h显著上调细胞Nox2, VPO1表达水平(P<0.01),并升高BNP、ANF、Ⅰ、Ⅲ型胶原纤维mRNA水平的表达(P<0.01),及纤维胶原含量。同时Ang Ⅱ能诱导H9c2细胞内H2O2和3-氯酪氨酸蛋白生成增加。NADPH氧化酶抑制剂DPI、catalase及VPO1抑制剂(ABAH)预处理可不同程度抑制Ang Ⅱ的上述作用。
(3) Ang Ⅱ诱导心肌细胞重构同时,能显著上调了MAPK (p-38、p-ERK、p-JNK)蛋白表达水平,DPI、catalase能不同程度抑制MAPK蛋白表达增加,但VPO1抑制剂仅能部分抑制Ang Ⅱ上调p-ERK蛋白表达。
结论：
VPO1至少部分介导了Ang Ⅱ诱导的心肌细胞重构,其机制可能涉及Nox2/H2O2/VPO1/HOC1/ERK1/2信号传导途径。
Background Cardiac remodeling in response to stress and injury, such as pressure or volume overload, neurohormones and cytokines, is characterized by cardiac hypertrophy and myocardial inflammation and fibrosis, which is a major risk factor for cardiovascular morbidity and mortality and a leading cause of chronic heart failure. A large body of evidence shows that oxidative stress plays an important role in the pathological process of cardiac remodeling. Stimulus mentioned above can activate the NADPH oxidases (NOX), a major resource of ROS, and result in large production of supreoxide (O2-) and peroxide (H2O2) with subsequent downstream of redox-sensitive signaling pathways, which is involved in the development of pathologic process of hypertrophy response and collagen deposition.
Vascμlar peroxidase1(VPO1) is a newly identified novel family member of peroxidases in cardiovascular system. VPO1as an enzyme that is downstream of NOX, functions to utilize NOX-derived hydrogen peroxide (H2O2) to produce a strong oxidant-hypochlorous acid (HOCl), and thus the oxidative stress is dramatically amplified. Several lines of evidence suggest that the NOX/VPO1pathway-mediated oxidative stress plays an important role in myocardial ischemia-reperfusion injury, endothelial cell apoptosis and smooth muscle cell proliferation. In addition, VPO1can be secreted into the extracellular space to participate in extracellular matrix formation, suggesting that VPO1may also play a role in cardiac remodeling, The present study was first to determine whether VPO1is implicated in hypertensive cardiac remodeling in vivo, and then to investigate whether VPO1is involved in Ang II induced cardiac remodeling in vitro and to explore the underlying mechanism.
Chapter I Relationship between VPO1and hypertensive cardiac remodeling
Objectives:To investigate the relationship between VPO1and hypertensive cardiac remodeling.
Methods:Twelve male spontaneously hypertensive rats (20-week-old) were served as hypertension group (SHR group), and Twelve male Wistar-Kyoto rats with the same age served as the normotensive control group (WKY group). Blood pressure was measured and after performing echocardiography analysis, the heart was isolated. Pathological changes of myocardial tissue was measured by HE staining, myocardial collagen deposition was measured by Masson staining, and the expression of VPO1was detected by immunohistochemistry。The expression of Nox2, Nox4and VPO1was also determined by western blot and the mRNA expression of type I Ⅲ collagen, Nox2、Nox4and VPO1was measured by real time-PCR.
Results:Compared with WKY group, blood pressure, thickness of ventricle, collagen deposition, mRNA and protein expression of Nox2、Nox4and VPO1, mRNA expression of type Ⅰ、Ⅲ collagen were all significantly increased in SHR group, whereas cardiac diastolic function is impaired in SHR group.
Conclusion:The present reserch indicates that VPO1may be involved in the process of Hypertensive rats cardiac remodeling via NOX/VP01-signaling pathways.
Chapter Ⅱ VPO1mediates Ang Ⅱ-induced myocardial remodeling in H9c2cells
Objective:To investigate whether VPO1mediates Ang Ⅱ-induced cardiac remodeling in H9c2cells and to explore the underlying mechanism.
Methods:(1) The effect of Ang Ⅱ on the VPO1expression in H9c2cells was observed. H9c2cells were treated with different concentrations of Ang Ⅱ (10-7M,10-6M,10-5M Ang Ⅱ) for24h, and H9c2cell were treated with Ang II for different time (12h,24h,48h). The expressions of VPO1were determined by Western-Blot and Real-Time PCR.(2) To study the effect of NADPH inhibitor diphenyleneio-donium (DPI), catalase, VPO1inhibitor-ABAH on Ang Ⅱ induced cardiac remodeling. Cultured H9c2cells were randomly divided into five groups:control group:cells were incubated in high glucose DMEM containing1%fetal bovine serum for24hours; Ang Ⅱ treatment group:cells were incubated in high glucose DMEM containing10-6M Ang II for24hours; Ang Ⅱ+DPI group:cells were pretreated with100μM DPI (NADPH oxidase inhibitor) for2hours prior to Ang II exposure; Ang Ⅱ+Catalase group: cells were pretreated with300μM Catalase for2hours prior to Ang II exposure; Ang II+ABAH group:cells were pretreated with400μM ABAH for2hours prior to Ang Ⅱ exposure; The mRNA and proteins expression of Nox2、Nox4and VPO1were determined by western blot and real time-PCR. Hypertrophy assay:H9c2cell were stained with crystal violet and the cellular size were calculated by Image software. Gene expression of BNP、ANF was tested by RT-PCR. Fibrosis assay: collagen type Ⅰ、Ⅲ gene expression was measured by RT-PCR, and collagen content was valued by Sirus Red staining. To explore the underlying mechanism:the protein expression of p-38、p-ERK and p-JNK were evaluated by western blot. The level of H2O2and HOC1were detected respectively through ELISA and3-chlorotyrosine protein immuno assay.
Results:
(1) In vitro, these results suggest that VPO1is unregulated by Ang II in a dose-depended manner, which can be abrogated both in gene and protein level by different inhibitors, such as NADPH inhibitors-DPI, catalase, and the VPO1inhibitors (aminobenzoic acid hydrazide, ABAH).
(2) Compared with the control group, Ang Ⅱ (10'6M) significantly increased the expression of Nox2, VPO1, the collagen content, the cellular size, and also up-regulated the gene expression of BNP, ANF, type In Ⅲ collagen. In addition, Ang II also increased the production of H2O2and the protein expression of3-chlorotyrosine protein. These effects of Ang II on H9c2cells were inhibited in a different degree by the pretreatment of DPI, catalase and the VPO1inhibitor (ABAH).
(3)Ang II induced myocardial remodeling, followed by up-regulating the MAPK (p-ERK, p-38, p-JNK) protein expression, which were attenuated by the NADPH oxidase inhibitor (DPI) and catalase. However, the VPOl inhibitor (ABAH) can only inhibit the up-regulation of p-ERK induced by Ang II.
Conclusion:
The present study has demonstrated that VPO1is at least part involved in the process of the Ang Ⅱ induced cardiac remodeling, both in myocardial hypertrophy and fibrosis. The results indicate that VPO1play a role via Nox2/H2O2/VPO1/HOCl/ERK1/2signaling pathway in the pathology of Ang Ⅱ induced cardiac remodeling.
引文
[1]Vasan R. S., Larson M. G., Benjamin E. J., et al. Congestive heart failure in subjects with normal versus reduced left ventricular ejection fraction: prevalence and mortality in a population-based cohort[J]. J Am Coll Cardiol,1999,33,7:1948-55.
[2]Lehnart S. E. Understanding the physiology of heart failure through cellular and in vivo models-towards targeting of complex mechanisms[J]. Exp Physiol,2013,98,3:622-8.
[3]Mann D. L. Mechanisms and models in heart failure:A combinatorial approach[J]. Circulation,1999,100,9:999-1008.
[4]Giordano F. J. Oxygen, oxidative stress, hypoxia, and heart failure[J]. J Clin Invest,2005,115,3:500-8.
[5]Tsutsui H., Kinugawa S. and Matsushima S. Oxidative stress and heart failure[J]. Am J Physiol Heart Circ Physiol,2011,301,6:H2181-90.
[6]Murdoch C. E., Zhang M., Cave A. C., et al. NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure [J]. Cardiovasc Res,2006,71,2:208-15.
[7]Li Y. Q., Li X. B., Guo S. J., et al. Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin Ⅱ-induced cardiac diastolic dysfunction in mice[J]. Acta Pharmacol Sin,2013,34,3:352-9.
[8]Essick E. E., Ouchi N., Wilson R. M., et al. Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling [J]. Am J Physiol Heart Circ Physiol,2011,301,3:H984-93.
[9]Cheng G., Salerno J. C., Cao Z., et al. Identification and characterization of VPO1, a new animal heme-containing peroxidase[J]. Free Radic Biol Med,2008,45,12:1682-94.
[10]Ma Q. L., Zhang G. G. and Peng J. Vascular Peroxidase 1:a Novel Enzyme in Promoting Oxidative Stress in Cardiovascular System[J]. Trends Cardiovasc Med,2013.
[11]Zhang Y. S., He L., Liu B., et al. A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia-reperfusion[J]. Basic Res Cardiol,2012,107,3:266.
[12]Bai Y. P., Hu C. P., Yuan Q., et al. Role of VPO1, a newly identified heme-containing peroxidase, in ox-LDL induced endothelial cell apoptosis[J]. Free Radic Biol Med,2011,51,8:1492-500.
[13]Shi R., Hu C., Yuan Q., et al. Involvement of vascular peroxidase 1 in angiotensin Ⅱ-induced vascular smooth muscle cell proliferation [J]. Cardiovasc Res,2011,91,1:27-36.
[14]Maulik S. K. and Kumar S. Oxidative stress and cardiac hypertrophy:a review[J]. Toxicol Mech Methods,2012,22,5:359-66.
[15]Ciardullo A. V., Azzolini L., Bevini M., et al. A diagnosis of left ventricular hypertrophy on ECG is associated with a high cardiovascular risk:findings from a 40- to 69-year-old cohort in general practice[J]. Fam Pract,2004,21, 1:63-5.
[16]Kenchaiah S. and Pfeffer M. A. Cardiac remodeling in systemic hypertension[J]. Med Clin North Am,2004,88,1:115-30.
[17]Matsubara L. S., Narikawa S., Ferreira A. L., et al. Myocardial remodeling in chronic pressure or volume overload in the rat heart[J]. Arq Bras Cardiol,2006,86,2:126-30.
[18]Tokuda K., Kai H., Kuwahara F., et al. Pressure-independent effects of angiotensin Ⅱ on hypertensive myocardial fibrosis[J]. Hypertension,2004,43, 2:499-503.
[19]Kai H., Kuwahara F., Tokuda K., et al. Diastolic dysfunction in hypertensive hearts:roles of perivascular inflammation and reactive myocardial fibrosis[J]. Hypertens Res,2005,28,6:483-90.
[20]Hutchinson K. R., Stewart J. A., Jr. and Lucchesi P. A. Extracellular matrix remodeling during the progression of volume overload-induced heart failure[J]. J Mol Cell Cardiol,2010,48,3:564-9.
[21]Yu H., Zhao G., Li H., et al. Candesartan antagonizes pressure overload-evoked cardiac remodeling through Smad7 gene-dependent MMP-9 suppression[J]. Gene,2012,497,2:301-6.
[22]Givvimani S., Kundu S., Narayanan N., et al. TIMP-2 mutant decreases MMP-2 activity and augments pressure overload induced LV dysfunction and heart failure[J]. Arch Physiol Biochem,2013.
[23]Lambeth J. D. NOX enzymes and the biology of reactive oxygen[J]. Nat Rev Immunol,2004,4,3:181-9.
[24]Kuroda J. and Sadoshima J. NADPH oxidase and cardiac failure [J]. J Cardiovasc Transl Res,2010,3,4:314-20.
[25]Liu Y., Huang H., Xia W., et al. NADPH oxidase inhibition ameliorates cardiac dysfunction in rabbits with heart failure [J]. Mol Cell Biochem,2010,343,1-2:143-53.
[26]Byrne J. A., Grieve D. J., Bendall J. K., et al. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy[J]. Circ Res,2003,93,9:802-5.
[27]Maytin M., Siwik D. A., Ito M., et al. Pressure overload-induced myocardial hypertrophy in mice does not require gp91phox[J]. Circulation,2004,109, 9:1168-71.
[28]Bendall J. K., Cave A. C., Heymes C., et al. Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin Ⅱ-induced cardiac hypertrophy in mice[J]. Circulation,2002,105,3:293-6.
[29]Liu P., Xu B., Cavalieri T. A., et al. Attenuation of antioxidative capacity enhances reperfusion injury in aged rat myocardium after MI/R[J]. Am J Physiol Heart Circ Physiol,2004,287,6:H2719-27.
[30]Sahna E., Deniz E., Bay-Karabulut A., et al. Melatonin protects myocardium from ischemia-reperfusion injury in hypertensive rats:role of myeloperoxidase activity[J]. Clin Exp Hypertens,2008,30,7:673-81.
[1]Azibani F., Fazal L., Chatziantoniou C., et al. [Hypertension-induced fibrosis: a balance story][J]. Ann Cardiol Angeiol (Paris),2012,61,3:150-5.
[2]Rohini A., Agrawal N., Koyani C. N., et al. Molecular targets and regulators of cardiac hypertrophy [J]. Pharmacol Res,2010,61,4:269-80.
[3]Murdoch C. E., Zhang M., Cave A. C., et al. NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure[J]. Cardiovasc Res,2006,71,2:208-15.
[4]De Mello W. C. and Danser A. H. Angiotensin II and the heart:on the intracrine renin-angiotensin system[J]. Hypertension,2000,35,6:1183-8.
[5]Verdecchia P., Angeli F., Mazzotta G., et al. The renin angiotensin system in the development of cardiovascular disease:role of aliskiren in risk reduction[J]. Vase Health Risk Manag,2008,4,5:971-81.
[6]Watkins S. J., Borthwick G. M. and Arthur H. M. The H9C2 cell line and primary neonatal cardiomyocyte cells show similar hypertrophic responses in vitro[J]. In Vitro Cell Dev Biol Anim,2011,47,2:125-31.
[7]Kimura S., Zhang G. X., Nishiyama A., et al. Role of NAD(P)H oxidase-and mitochondria-derived reactive oxygen species in cardioprotection of ischemic reperfusion injury by angiotensin Ⅱ[J]. Hypertension,2005,45, 5:860-6.
[8]Kwon S. H., Pimentel D. R., Remondino A., et al. H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways[J]. J Mol Cell Cardiol,2003,35,6:615-21.
[9]Griendling K. K., Sorescu D. and Ushio-Fukai M. NAD(P)H oxidase:role in cardiovascular biology and disease[J]. Circ Res,2000,86,5:494-501.
[10]Purcell N. H., Tang G., Yu C., et al. Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes[J]. Proc Natl Acad Sci U S A,2001,98,12:6668-73.
[11]Cheng G., Salerno J. C., Cao Z., et al. Identification and characterization of VPO1, a new animal heme-containing peroxidase[J]. Free Radic Biol Med,2008,45,12:1682-94.
[12]Han L., Shen X., Pan L., et al. Aminobenzoic acid hydrazide, a myeloperoxidase inhibitor, alters the adhesive properties of neutrophils isolated from acute myocardial infarction patients[J]. Heart Vessels,2012,27, 5:468-74.
[13]Li T. T., Zhang Y. S., He L., et al. Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion[J]. Can J Physiol Pharmacol,2012,90,7:851-62.
[14]Bai Y. P., Hu C. P., Yuan Q., et al. Role of VPO1, a newly identified heme-containing peroxidase, in ox-LDL induced endothelial cell apoptosis[J]. Free Radic Biol Med,2011,51,8:1492-500.
[15]Shi R., Hu C., Yuan Q., et al. Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation[J]. Cardiovasc Res,2011,91,1:27-36.
[16]Gao L. and Mann G. E. Vascular NAD(P)H oxidase activation in diabetes:a double-edged sword in redox signalling [J]. Cardiovasc Res,2009,82,1:9-20.
[17]Hori M. and Nishida K. Oxidative stress and left ventricular remodelling after myocardial infarction [J]. Cardiovasc Res,2009,81,3:457-64.
[18]Puddu P., Puddu G. M., Cravero E., et al. The molecular sources of reactive oxygen species in hypertension [J]. Blood Press,2008,17,2:70-7.
[19]Nakamura K., Fushimi K., Kouchi H., et al. Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-alpha and angiotensin Ⅱ[J]. Circulation,1998,98,8:794-9.
[20]Bendall J. K., Cave A. C., Heymes C., et al. Pivotal role of a gp91 (phox)-containing NADPH oxidase in angiotensin Ⅱ-induced cardiac hypertrophy in mice[J]. Circulation,2002,105,3:293-6.
[21]Luchtefeld M., Grote K., Grothusen C., et al. Angiotensin Ⅱ induces MMP-2 in a p47phox-dependent manner[J]. Biochem Biophys Res Commun,2005,328,1:183-8.
[22]Siwik D. A., Pagano P. J. and Colucci W. S. Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts[J]. Am J Physiol Cell Physiol,2001,280,1:C53-60.
[23]Viappiani S., Nicolescu A. C., Holt A., et al. Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione[J]. Biochem Pharmacol,2009,77,5:826-34.
[24]Ali M. A. and Schulz R. Activation of MMP-2 as a key event in oxidative stress injury to the heart[J]. Front Biosci,2009,14:699-716.
[25]Huang X. R., Chung A. C., Yang F., et al. Smad3 mediates cardiac inflammation and fibrosis in angiotensin Ⅱ-induced hypertensive cardiac remodeling[J]. Hypertension,2010,55,5:1165-71.
[26]Dworakowski R., Anilkumar N., Zhang M., et al. Redox signalling involving NADPH oxidase-derived reactive oxygen species[J]. Biochem Soc Trans,2006,34, Pt 5:960-4.
[27]Sugden P. H. and Clerk A. Regulation of mitogen-activated protein kinase cascades in the heart[J]. Adv Enzyme Regul,1998,38:87-98.
[28]Essick E. E., Ouchi N., Wilson R. M., et al. Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling [J]. Am J Physiol Heart Circ Physiol,2011,301,3:H984-93.
[29]Bueno O. F., De Windt L. J., Tymitz K. M., et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice[J]. EMBO J,2000,19,23:6341-50.
[1]Brilla C. G., Matsubara L. and Weber K. T. Advanced hypertensive heart disease in spontaneously hypertensive rats. Lisinopril-mediated regression of myocardial fibrosis[J]. Hypertension,1996,28,2:269-75.
[2]Weber K. T. Targeting pathological remodeling:concepts of cardioprotection and reparation[J]. Circulation,2000,102,12:1342-5.
[3]Weber K. T. and Brilla C. G. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system[J]. Circulation,1991,83,6:1849-65.
[4]Diez J. Mechanisms of cardiac fibrosis in hypertension[J]. J Clin Hypertens (Greenwich),2007,9,7:546-50.
[5]Werner C. M. and Bohm M. The therapeutic role of RAS blockade in chronic heart failure[J]. Ther Adv Cardiovasc Dis,2008,2,3:167-77.
[6]Ferrario C. M. and Strawn W. B. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease [J]. Am J Cardiol,2006,98,1:121-8.
[7]Tschope C., Schultheiss H. P. and Walther T. Multiple interactions between the renin-angiotensin and the kallikrein-kinin systems:role of ACE inhibition and AT1 receptor blockade[J]. J Cardiovasc Pharmacol,2002,39, 4:478-87.
[8]Berry C., Touyz R., Dominiczak A. F., et al. Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide[J]. Am J Physiol Heart Circ Physiol,2001,281,6:H2337-65.
[9]Mehta P. K. and Griendling K. K. Angiotensin Ⅱ cell signaling: physiological and pathological effects in the cardiovascular system[J]. Am J Physiol Cell Physiol,2007,292, 1:C82-97.
[10]Touyz R. M. and Schiffrin E. L. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin Ⅱ in vascular smooth muscle cells[J]. Pharmacol Rev,2000,52,4:639-72.
[11]Griendling K. K., Minieri C. A., Ollerenshaw J. D., et al. Angiotensin Ⅱ stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells[J]. Circ Res,1994,74,6:1141-8.
[12]Lijnen P., Papparella I., Petrov V., et al. Angiotensin Ⅱ-stimulated collagen production in cardiac fibroblasts is mediated by reactive oxygen species[J]. J Hypertens,2006,24,4:757-66.
[13]Sano M., Fukuda K., Sato T., et al. ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin Ⅱ in cardiac fibroblasts[J]. Circ Res,2001,89,8:661-9.
[14]Ushio-Fukai M., Alexander R. W., Akers M., et al. p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin Ⅱ. Role in vascular smooth muscle cell hypertrophy [J]. J Biol Chem,1998,273,24:15022-9.
[15]Li N. and Karin M. Is NF-kappaB the sensor of oxidative stress?[J]. FASEB J,1999,13,10:1137-43.
[16]Touyz R. M. Reactive oxygen species as mediators of calcium signaling by angiotensin II:implications in vascular physiology and pathophysiology [J]. Antioxid Redox Signal,2005,7,9-10:1302-14.
[17]Touyz R. M., He G., El Mabrouk M., et al. p38 Map kinase regulates vascular smooth muscle cell collagen synthesis by angiotensin Ⅱ in SHR but not in WKY[J]. Hypertension,2001,37,2 Pt2:574-80.
[18]Shivakumar K. and Kumaran C. L-type calcium channel blockers and EGTA enhance superoxide production in cardiac fibroblasts[J]. J Mol Cell Cardiol,2001,33,2:373-7.
[19]Stolk J., Hiltermann T. J., Dijkman J. H., et al. Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol[J]. Am J Respir Cell Mol Biol,1994.11, 1:95-102.
[20]Doussiere J. and Vignais P. V. Diphenylene iodonium as an inhibitor of the NADPH oxidase complex of bovine neutrophils. Factors controlling the inhibitory potency of diphenylene iodonium in a cell-free system of oxidase activation[J]. Eur J Biochem,1992,208,1:61-71.
[21]Cowling R. T., Gurantz D., Peng J., et al. Transcription factor NF-kappa B is necessary for up-regulation of type 1 angiotensin Ⅱ receptor mRNA in rat cardiac fibroblasts treated with tumor necrosis factor-alpha or interleukin-1 beta[J]. J Biol Chem,2002,277,8:5719-24.
[22]Bataller R., Gabele E., Schoonhoven R., et al. Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and pro inflammatory events in liver [J]. Am J Physiol Gastrointest Liver Physiol,2003,285,3:G642-51.
[23]Recinos A.,3rd, LeJeune W. S., Sun H., et al. Angiotensin Ⅱ induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice[J]. Atherosclerosis,2007,194,1:125-33.
[24]Kang Y. M., Ma Y., Zheng J. P., et al. Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin Ⅱ-induced hypertension[J]. Cardiovasc Res,2009,82,3:503-12.
[25]Gurantz D., Cowling R. T., Varki N., et al. IL-lbeta and TNF-alpha upregulate angiotensin Ⅱ type 1 (AT1) receptors on cardiac fibroblasts and are associated with increased AT1 density in the post-MI heart[J]. J Mol Cell Cardiol,2005,38,3:505-15.
[26]Kadokami T., Frye C., Lemster B., et al. Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic model[J]. Circulation.2001,104, 10:1094-7.
[27]Sun M., Dawood F., Wen W. H., et al. Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction[J]. Circulation,2004,110,20:3221-8.
[28]Bujak M., Dobaczewski M., Chatila K., et al. Interleukin-1 receptor type Ⅰ signaling critically regulates infarct healing and cardiac remodeling[J]. Am J Pathol,2008,173,1:57-67.
[29]Coles B., Fielding C. A., Rose-John S., et al. Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo[J]. Am J Pathol,2007,171,1:315-25.
[30]Ogawa S., Kobori H., Ohashi N., et al. Angiotensin Ⅱ Type 1 Receptor Blockers Reduce Urinary Angiotensinogen Excretion and the Levels of Urinary Markers of Oxidative Stress and Inflammation in Patients with Type 2 Diabetic Nephropathy[J]. Biomark Insights,2009,4:97-102.
[31]Zemse S. M., Hilgers R. H. and Webb R. C. Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG Ⅱ in murine aortic rings[J]. Am J Physiol Heart Circ Physiol,2007,292,6:H3103-8.
[32]Didion S. P., Kinzenbaw D. A., Schrader L. I., et al. Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction[J]. Hypertension,2009,54,3:619-24.
[33]Pasqui A. L.. Di Renzo M., Maffei S., et al. Pro/Anti-inflammatory cytokine imbalance in postischemic left ventricular remodeling[J]. Mediators Inflamm,2010,2010:974694.
[34]Collins A. R., Schnee J., Wang W., et al. Osteopontin modulates angiotensin II-induced fibrosis in the intact murine heart[J]. J Am Coll Cardiol,2004,43, 9:1698-705.
[35]Ma Y., Zhang L., Peng T., et al. Angiotensin Ⅱ stimulates transcription of insulin-like growth factor I receptor in vascular smooth muscle cells:role of nuclear factor-kappaB[J]. Endocrinology,2006,147,3:1256-63.
[36]Zhan Y., Brown C., Maynard E., et al. Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling[J]. J Clin Invest,2005,115, 9:2508-16.
[37]Nishida M., Kitajima N., Saiki S., et al. Regulation of Angiotensin Ⅱ receptor signaling by cysteine modification of NF-kappaB[J]. Nitric Oxide,2011,25,2:112-7.
[38]Whaley-Connell A., Govindarajan G., Habibi J., et al. Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in the transgenic (mRen2) 27 Ren2 rat[J]. Am J Physiol Endocrinol Metab,2007,293, 1:E355-63.
[39]Oudit G. Y., Kassiri Z., Patel M. P., et al. Angiotensin Ⅱ-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice[J]. Cardiovasc Res,2007,75,1:29-39.
[40]Yamamoto E., Kataoka K., Shintaku H., et al. Novel mechanism and role of angiotensin Ⅱ induced vascular endothelial injury in hypertensive diastolic heart failure[J]. Arterioscler Thromb Vasc Biol,2007,27,12:2569-75.
[41]Usui M. and Egashira K. [Angiotensin Ⅱ receptor and oxidative stress][J]. Nihon Rinsho,2002,60,10:1893-7.
[42]McAllister-Lucas L. M., Jin X., Gu S., et al. The CARMA3-Bc110-MALT1 signalosome promotes angiotensin II-dependent vascular inflammation and atherogenesis[J]. J Biol Chem,2010,285,34:25880-4.
[43]Tummala P. E., Chen X. L., Sundell C. L., et al. Angiotensin Ⅱ induces vascular cell adhesion molecule-1 expression in rat vasculature:A potential link between the renin-angiotensin system and atherosclerosis[J]. Circulation,1999,100,11:1223-9.
[44]Doughan A. K., Harrison D. G. and Dikalov S. I. Molecular mechanisms of angiotensin Ⅱ-mediated mitochondrial dysfunction:linking mitochondrial oxidative damage and vascular endothelial dysfunction[J]. Circ Res,2008,102,4:488-96.
[45]Zahradka P., Werner J. P., Buhay S., et al. NF-kappaB activation is essential for angiotensin Ⅱ-dependent proliferation and migration of vascular smooth muscle cells[J]. J Mol Cell Cardiol,2002,34,12:1609-21.
[46]Masur S. K., Dewal H. S., Dinh T. T., et al. Myofibroblasts differentiate from fibroblasts when plated at low density [J]. Proc Natl Acad Sci U S A,1996,93,9:4219-23.
[47]Haudek S. B., Xia Y., Huebener P., et al. Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice[J]. Proc Natl Acad Sci U S A,2006,103,48:18284-9.
[48]Haudek S. B., Cheng J., Du J., et al. Monocytic fibroblast precursors mediate fibrosis in angiotensin-Ⅱ-induced cardiac hypertrophy [J]. J Mol Cell Cardiol,2010,49,3:499-507.
[49]Arciniegas E., Frid M. G., Douglas I. S., et al. Perspectives on endothelial-to-mesenchymal transition:potential contribution to vascular remodeling in chronic pulmonary hypertension[J]. Am J Physiol Lung Cell Mol Physiol,2007,293, 1:L1-8.
[2]Lehnart S. E. Understanding the physiology of heart failure through cellular and in vivo models-towards targeting of complex mechanisms[J]. Exp Physiol,2013,98,3:622-8.
[3]Mann D. L. Mechanisms and models in heart failure:A combinatorial approach[J]. Circulation,1999,100,9:999-1008.
[4]Giordano F. J. Oxygen, oxidative stress, hypoxia, and heart failure[J]. J Clin Invest,2005,115,3:500-8.
[5]Tsutsui H., Kinugawa S. and Matsushima S. Oxidative stress and heart failure[J]. Am J Physiol Heart Circ Physiol,2011,301,6:H2181-90.
[6]Murdoch C. E., Zhang M., Cave A. C., et al. NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure [J]. Cardiovasc Res,2006,71,2:208-15.
[7]Li Y. Q., Li X. B., Guo S. J., et al. Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin Ⅱ-induced cardiac diastolic dysfunction in mice[J]. Acta Pharmacol Sin,2013,34,3:352-9.
[8]Essick E. E., Ouchi N., Wilson R. M., et al. Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling [J]. Am J Physiol Heart Circ Physiol,2011,301,3:H984-93.
[9]Cheng G., Salerno J. C., Cao Z., et al. Identification and characterization of VPO1, a new animal heme-containing peroxidase[J]. Free Radic Biol Med,2008,45,12:1682-94.
[10]Ma Q. L., Zhang G. G. and Peng J. Vascular Peroxidase 1:a Novel Enzyme in Promoting Oxidative Stress in Cardiovascular System[J]. Trends Cardiovasc Med,2013.
[11]Zhang Y. S., He L., Liu B., et al. A novel pathway of NADPH oxidase/vascular peroxidase 1 in mediating oxidative injury following ischemia-reperfusion[J]. Basic Res Cardiol,2012,107,3:266.
[12]Bai Y. P., Hu C. P., Yuan Q., et al. Role of VPO1, a newly identified heme-containing peroxidase, in ox-LDL induced endothelial cell apoptosis[J]. Free Radic Biol Med,2011,51,8:1492-500.
[13]Shi R., Hu C., Yuan Q., et al. Involvement of vascular peroxidase 1 in angiotensin Ⅱ-induced vascular smooth muscle cell proliferation [J]. Cardiovasc Res,2011,91,1:27-36.
[14]Maulik S. K. and Kumar S. Oxidative stress and cardiac hypertrophy:a review[J]. Toxicol Mech Methods,2012,22,5:359-66.
[15]Ciardullo A. V., Azzolini L., Bevini M., et al. A diagnosis of left ventricular hypertrophy on ECG is associated with a high cardiovascular risk:findings from a 40- to 69-year-old cohort in general practice[J]. Fam Pract,2004,21, 1:63-5.
[16]Kenchaiah S. and Pfeffer M. A. Cardiac remodeling in systemic hypertension[J]. Med Clin North Am,2004,88,1:115-30.
[17]Matsubara L. S., Narikawa S., Ferreira A. L., et al. Myocardial remodeling in chronic pressure or volume overload in the rat heart[J]. Arq Bras Cardiol,2006,86,2:126-30.
[18]Tokuda K., Kai H., Kuwahara F., et al. Pressure-independent effects of angiotensin Ⅱ on hypertensive myocardial fibrosis[J]. Hypertension,2004,43, 2:499-503.
[19]Kai H., Kuwahara F., Tokuda K., et al. Diastolic dysfunction in hypertensive hearts:roles of perivascular inflammation and reactive myocardial fibrosis[J]. Hypertens Res,2005,28,6:483-90.
[20]Hutchinson K. R., Stewart J. A., Jr. and Lucchesi P. A. Extracellular matrix remodeling during the progression of volume overload-induced heart failure[J]. J Mol Cell Cardiol,2010,48,3:564-9.
[21]Yu H., Zhao G., Li H., et al. Candesartan antagonizes pressure overload-evoked cardiac remodeling through Smad7 gene-dependent MMP-9 suppression[J]. Gene,2012,497,2:301-6.
[22]Givvimani S., Kundu S., Narayanan N., et al. TIMP-2 mutant decreases MMP-2 activity and augments pressure overload induced LV dysfunction and heart failure[J]. Arch Physiol Biochem,2013.
[23]Lambeth J. D. NOX enzymes and the biology of reactive oxygen[J]. Nat Rev Immunol,2004,4,3:181-9.
[24]Kuroda J. and Sadoshima J. NADPH oxidase and cardiac failure [J]. J Cardiovasc Transl Res,2010,3,4:314-20.
[25]Liu Y., Huang H., Xia W., et al. NADPH oxidase inhibition ameliorates cardiac dysfunction in rabbits with heart failure [J]. Mol Cell Biochem,2010,343,1-2:143-53.
[26]Byrne J. A., Grieve D. J., Bendall J. K., et al. Contrasting roles of NADPH oxidase isoforms in pressure-overload versus angiotensin II-induced cardiac hypertrophy[J]. Circ Res,2003,93,9:802-5.
[27]Maytin M., Siwik D. A., Ito M., et al. Pressure overload-induced myocardial hypertrophy in mice does not require gp91phox[J]. Circulation,2004,109, 9:1168-71.
[28]Bendall J. K., Cave A. C., Heymes C., et al. Pivotal role of a gp91(phox)-containing NADPH oxidase in angiotensin Ⅱ-induced cardiac hypertrophy in mice[J]. Circulation,2002,105,3:293-6.
[29]Liu P., Xu B., Cavalieri T. A., et al. Attenuation of antioxidative capacity enhances reperfusion injury in aged rat myocardium after MI/R[J]. Am J Physiol Heart Circ Physiol,2004,287,6:H2719-27.
[30]Sahna E., Deniz E., Bay-Karabulut A., et al. Melatonin protects myocardium from ischemia-reperfusion injury in hypertensive rats:role of myeloperoxidase activity[J]. Clin Exp Hypertens,2008,30,7:673-81.
[1]Azibani F., Fazal L., Chatziantoniou C., et al. [Hypertension-induced fibrosis: a balance story][J]. Ann Cardiol Angeiol (Paris),2012,61,3:150-5.
[2]Rohini A., Agrawal N., Koyani C. N., et al. Molecular targets and regulators of cardiac hypertrophy [J]. Pharmacol Res,2010,61,4:269-80.
[3]Murdoch C. E., Zhang M., Cave A. C., et al. NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure[J]. Cardiovasc Res,2006,71,2:208-15.
[4]De Mello W. C. and Danser A. H. Angiotensin II and the heart:on the intracrine renin-angiotensin system[J]. Hypertension,2000,35,6:1183-8.
[5]Verdecchia P., Angeli F., Mazzotta G., et al. The renin angiotensin system in the development of cardiovascular disease:role of aliskiren in risk reduction[J]. Vase Health Risk Manag,2008,4,5:971-81.
[6]Watkins S. J., Borthwick G. M. and Arthur H. M. The H9C2 cell line and primary neonatal cardiomyocyte cells show similar hypertrophic responses in vitro[J]. In Vitro Cell Dev Biol Anim,2011,47,2:125-31.
[7]Kimura S., Zhang G. X., Nishiyama A., et al. Role of NAD(P)H oxidase-and mitochondria-derived reactive oxygen species in cardioprotection of ischemic reperfusion injury by angiotensin Ⅱ[J]. Hypertension,2005,45, 5:860-6.
[8]Kwon S. H., Pimentel D. R., Remondino A., et al. H(2)O(2) regulates cardiac myocyte phenotype via concentration-dependent activation of distinct kinase pathways[J]. J Mol Cell Cardiol,2003,35,6:615-21.
[9]Griendling K. K., Sorescu D. and Ushio-Fukai M. NAD(P)H oxidase:role in cardiovascular biology and disease[J]. Circ Res,2000,86,5:494-501.
[10]Purcell N. H., Tang G., Yu C., et al. Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes[J]. Proc Natl Acad Sci U S A,2001,98,12:6668-73.
[11]Cheng G., Salerno J. C., Cao Z., et al. Identification and characterization of VPO1, a new animal heme-containing peroxidase[J]. Free Radic Biol Med,2008,45,12:1682-94.
[12]Han L., Shen X., Pan L., et al. Aminobenzoic acid hydrazide, a myeloperoxidase inhibitor, alters the adhesive properties of neutrophils isolated from acute myocardial infarction patients[J]. Heart Vessels,2012,27, 5:468-74.
[13]Li T. T., Zhang Y. S., He L., et al. Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion[J]. Can J Physiol Pharmacol,2012,90,7:851-62.
[14]Bai Y. P., Hu C. P., Yuan Q., et al. Role of VPO1, a newly identified heme-containing peroxidase, in ox-LDL induced endothelial cell apoptosis[J]. Free Radic Biol Med,2011,51,8:1492-500.
[15]Shi R., Hu C., Yuan Q., et al. Involvement of vascular peroxidase 1 in angiotensin II-induced vascular smooth muscle cell proliferation[J]. Cardiovasc Res,2011,91,1:27-36.
[16]Gao L. and Mann G. E. Vascular NAD(P)H oxidase activation in diabetes:a double-edged sword in redox signalling [J]. Cardiovasc Res,2009,82,1:9-20.
[17]Hori M. and Nishida K. Oxidative stress and left ventricular remodelling after myocardial infarction [J]. Cardiovasc Res,2009,81,3:457-64.
[18]Puddu P., Puddu G. M., Cravero E., et al. The molecular sources of reactive oxygen species in hypertension [J]. Blood Press,2008,17,2:70-7.
[19]Nakamura K., Fushimi K., Kouchi H., et al. Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-alpha and angiotensin Ⅱ[J]. Circulation,1998,98,8:794-9.
[20]Bendall J. K., Cave A. C., Heymes C., et al. Pivotal role of a gp91 (phox)-containing NADPH oxidase in angiotensin Ⅱ-induced cardiac hypertrophy in mice[J]. Circulation,2002,105,3:293-6.
[21]Luchtefeld M., Grote K., Grothusen C., et al. Angiotensin Ⅱ induces MMP-2 in a p47phox-dependent manner[J]. Biochem Biophys Res Commun,2005,328,1:183-8.
[22]Siwik D. A., Pagano P. J. and Colucci W. S. Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts[J]. Am J Physiol Cell Physiol,2001,280,1:C53-60.
[23]Viappiani S., Nicolescu A. C., Holt A., et al. Activation and modulation of 72kDa matrix metalloproteinase-2 by peroxynitrite and glutathione[J]. Biochem Pharmacol,2009,77,5:826-34.
[24]Ali M. A. and Schulz R. Activation of MMP-2 as a key event in oxidative stress injury to the heart[J]. Front Biosci,2009,14:699-716.
[25]Huang X. R., Chung A. C., Yang F., et al. Smad3 mediates cardiac inflammation and fibrosis in angiotensin Ⅱ-induced hypertensive cardiac remodeling[J]. Hypertension,2010,55,5:1165-71.
[26]Dworakowski R., Anilkumar N., Zhang M., et al. Redox signalling involving NADPH oxidase-derived reactive oxygen species[J]. Biochem Soc Trans,2006,34, Pt 5:960-4.
[27]Sugden P. H. and Clerk A. Regulation of mitogen-activated protein kinase cascades in the heart[J]. Adv Enzyme Regul,1998,38:87-98.
[28]Essick E. E., Ouchi N., Wilson R. M., et al. Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling [J]. Am J Physiol Heart Circ Physiol,2011,301,3:H984-93.
[29]Bueno O. F., De Windt L. J., Tymitz K. M., et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice[J]. EMBO J,2000,19,23:6341-50.
[1]Brilla C. G., Matsubara L. and Weber K. T. Advanced hypertensive heart disease in spontaneously hypertensive rats. Lisinopril-mediated regression of myocardial fibrosis[J]. Hypertension,1996,28,2:269-75.
[2]Weber K. T. Targeting pathological remodeling:concepts of cardioprotection and reparation[J]. Circulation,2000,102,12:1342-5.
[3]Weber K. T. and Brilla C. G. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system[J]. Circulation,1991,83,6:1849-65.
[4]Diez J. Mechanisms of cardiac fibrosis in hypertension[J]. J Clin Hypertens (Greenwich),2007,9,7:546-50.
[5]Werner C. M. and Bohm M. The therapeutic role of RAS blockade in chronic heart failure[J]. Ther Adv Cardiovasc Dis,2008,2,3:167-77.
[6]Ferrario C. M. and Strawn W. B. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease [J]. Am J Cardiol,2006,98,1:121-8.
[7]Tschope C., Schultheiss H. P. and Walther T. Multiple interactions between the renin-angiotensin and the kallikrein-kinin systems:role of ACE inhibition and AT1 receptor blockade[J]. J Cardiovasc Pharmacol,2002,39, 4:478-87.
[8]Berry C., Touyz R., Dominiczak A. F., et al. Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide[J]. Am J Physiol Heart Circ Physiol,2001,281,6:H2337-65.
[9]Mehta P. K. and Griendling K. K. Angiotensin Ⅱ cell signaling: physiological and pathological effects in the cardiovascular system[J]. Am J Physiol Cell Physiol,2007,292, 1:C82-97.
[10]Touyz R. M. and Schiffrin E. L. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin Ⅱ in vascular smooth muscle cells[J]. Pharmacol Rev,2000,52,4:639-72.
[11]Griendling K. K., Minieri C. A., Ollerenshaw J. D., et al. Angiotensin Ⅱ stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells[J]. Circ Res,1994,74,6:1141-8.
[12]Lijnen P., Papparella I., Petrov V., et al. Angiotensin Ⅱ-stimulated collagen production in cardiac fibroblasts is mediated by reactive oxygen species[J]. J Hypertens,2006,24,4:757-66.
[13]Sano M., Fukuda K., Sato T., et al. ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen species-mediated induction of IL-6 by angiotensin Ⅱ in cardiac fibroblasts[J]. Circ Res,2001,89,8:661-9.
[14]Ushio-Fukai M., Alexander R. W., Akers M., et al. p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin Ⅱ. Role in vascular smooth muscle cell hypertrophy [J]. J Biol Chem,1998,273,24:15022-9.
[15]Li N. and Karin M. Is NF-kappaB the sensor of oxidative stress?[J]. FASEB J,1999,13,10:1137-43.
[16]Touyz R. M. Reactive oxygen species as mediators of calcium signaling by angiotensin II:implications in vascular physiology and pathophysiology [J]. Antioxid Redox Signal,2005,7,9-10:1302-14.
[17]Touyz R. M., He G., El Mabrouk M., et al. p38 Map kinase regulates vascular smooth muscle cell collagen synthesis by angiotensin Ⅱ in SHR but not in WKY[J]. Hypertension,2001,37,2 Pt2:574-80.
[18]Shivakumar K. and Kumaran C. L-type calcium channel blockers and EGTA enhance superoxide production in cardiac fibroblasts[J]. J Mol Cell Cardiol,2001,33,2:373-7.
[19]Stolk J., Hiltermann T. J., Dijkman J. H., et al. Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol[J]. Am J Respir Cell Mol Biol,1994.11, 1:95-102.
[20]Doussiere J. and Vignais P. V. Diphenylene iodonium as an inhibitor of the NADPH oxidase complex of bovine neutrophils. Factors controlling the inhibitory potency of diphenylene iodonium in a cell-free system of oxidase activation[J]. Eur J Biochem,1992,208,1:61-71.
[21]Cowling R. T., Gurantz D., Peng J., et al. Transcription factor NF-kappa B is necessary for up-regulation of type 1 angiotensin Ⅱ receptor mRNA in rat cardiac fibroblasts treated with tumor necrosis factor-alpha or interleukin-1 beta[J]. J Biol Chem,2002,277,8:5719-24.
[22]Bataller R., Gabele E., Schoonhoven R., et al. Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and pro inflammatory events in liver [J]. Am J Physiol Gastrointest Liver Physiol,2003,285,3:G642-51.
[23]Recinos A.,3rd, LeJeune W. S., Sun H., et al. Angiotensin Ⅱ induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice[J]. Atherosclerosis,2007,194,1:125-33.
[24]Kang Y. M., Ma Y., Zheng J. P., et al. Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin Ⅱ-induced hypertension[J]. Cardiovasc Res,2009,82,3:503-12.
[25]Gurantz D., Cowling R. T., Varki N., et al. IL-lbeta and TNF-alpha upregulate angiotensin Ⅱ type 1 (AT1) receptors on cardiac fibroblasts and are associated with increased AT1 density in the post-MI heart[J]. J Mol Cell Cardiol,2005,38,3:505-15.
[26]Kadokami T., Frye C., Lemster B., et al. Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic model[J]. Circulation.2001,104, 10:1094-7.
[27]Sun M., Dawood F., Wen W. H., et al. Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction[J]. Circulation,2004,110,20:3221-8.
[28]Bujak M., Dobaczewski M., Chatila K., et al. Interleukin-1 receptor type Ⅰ signaling critically regulates infarct healing and cardiac remodeling[J]. Am J Pathol,2008,173,1:57-67.
[29]Coles B., Fielding C. A., Rose-John S., et al. Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo[J]. Am J Pathol,2007,171,1:315-25.
[30]Ogawa S., Kobori H., Ohashi N., et al. Angiotensin Ⅱ Type 1 Receptor Blockers Reduce Urinary Angiotensinogen Excretion and the Levels of Urinary Markers of Oxidative Stress and Inflammation in Patients with Type 2 Diabetic Nephropathy[J]. Biomark Insights,2009,4:97-102.
[31]Zemse S. M., Hilgers R. H. and Webb R. C. Interleukin-10 counteracts impaired endothelium-dependent relaxation induced by ANG Ⅱ in murine aortic rings[J]. Am J Physiol Heart Circ Physiol,2007,292,6:H3103-8.
[32]Didion S. P., Kinzenbaw D. A., Schrader L. I., et al. Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction[J]. Hypertension,2009,54,3:619-24.
[33]Pasqui A. L.. Di Renzo M., Maffei S., et al. Pro/Anti-inflammatory cytokine imbalance in postischemic left ventricular remodeling[J]. Mediators Inflamm,2010,2010:974694.
[34]Collins A. R., Schnee J., Wang W., et al. Osteopontin modulates angiotensin II-induced fibrosis in the intact murine heart[J]. J Am Coll Cardiol,2004,43, 9:1698-705.
[35]Ma Y., Zhang L., Peng T., et al. Angiotensin Ⅱ stimulates transcription of insulin-like growth factor I receptor in vascular smooth muscle cells:role of nuclear factor-kappaB[J]. Endocrinology,2006,147,3:1256-63.
[36]Zhan Y., Brown C., Maynard E., et al. Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling[J]. J Clin Invest,2005,115, 9:2508-16.
[37]Nishida M., Kitajima N., Saiki S., et al. Regulation of Angiotensin Ⅱ receptor signaling by cysteine modification of NF-kappaB[J]. Nitric Oxide,2011,25,2:112-7.
[38]Whaley-Connell A., Govindarajan G., Habibi J., et al. Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in the transgenic (mRen2) 27 Ren2 rat[J]. Am J Physiol Endocrinol Metab,2007,293, 1:E355-63.
[39]Oudit G. Y., Kassiri Z., Patel M. P., et al. Angiotensin Ⅱ-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice[J]. Cardiovasc Res,2007,75,1:29-39.
[40]Yamamoto E., Kataoka K., Shintaku H., et al. Novel mechanism and role of angiotensin Ⅱ induced vascular endothelial injury in hypertensive diastolic heart failure[J]. Arterioscler Thromb Vasc Biol,2007,27,12:2569-75.
[41]Usui M. and Egashira K. [Angiotensin Ⅱ receptor and oxidative stress][J]. Nihon Rinsho,2002,60,10:1893-7.
[42]McAllister-Lucas L. M., Jin X., Gu S., et al. The CARMA3-Bc110-MALT1 signalosome promotes angiotensin II-dependent vascular inflammation and atherogenesis[J]. J Biol Chem,2010,285,34:25880-4.
[43]Tummala P. E., Chen X. L., Sundell C. L., et al. Angiotensin Ⅱ induces vascular cell adhesion molecule-1 expression in rat vasculature:A potential link between the renin-angiotensin system and atherosclerosis[J]. Circulation,1999,100,11:1223-9.
[44]Doughan A. K., Harrison D. G. and Dikalov S. I. Molecular mechanisms of angiotensin Ⅱ-mediated mitochondrial dysfunction:linking mitochondrial oxidative damage and vascular endothelial dysfunction[J]. Circ Res,2008,102,4:488-96.
[45]Zahradka P., Werner J. P., Buhay S., et al. NF-kappaB activation is essential for angiotensin Ⅱ-dependent proliferation and migration of vascular smooth muscle cells[J]. J Mol Cell Cardiol,2002,34,12:1609-21.
[46]Masur S. K., Dewal H. S., Dinh T. T., et al. Myofibroblasts differentiate from fibroblasts when plated at low density [J]. Proc Natl Acad Sci U S A,1996,93,9:4219-23.
[47]Haudek S. B., Xia Y., Huebener P., et al. Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice[J]. Proc Natl Acad Sci U S A,2006,103,48:18284-9.
[48]Haudek S. B., Cheng J., Du J., et al. Monocytic fibroblast precursors mediate fibrosis in angiotensin-Ⅱ-induced cardiac hypertrophy [J]. J Mol Cell Cardiol,2010,49,3:499-507.
[49]Arciniegas E., Frid M. G., Douglas I. S., et al. Perspectives on endothelial-to-mesenchymal transition:potential contribution to vascular remodeling in chronic pulmonary hypertension[J]. Am J Physiol Lung Cell Mol Physiol,2007,293, 1:L1-8.
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