高密度脂蛋白功能与心血管疾病
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摘要
正常高密度脂蛋白(high-density lipoprotein,HDL)具有保护心血管的作用。但随着研究的深入,尤其是针对HDL代谢相关基因突变群体的研究和升高高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)的药物研究失败后,HDL-C与心血管疾病的关系变得扑朔迷离。研究发现正常状态下HDL不仅有逆转运胆固醇(reverse cholesterol transport,RCT)的作用,还有抗氧化、抗炎、促进血管新生等作用,而疾病状态下HDL会失去保护作用甚至损害心血管功能。关于HDL的研究从HDL-C水平转移至HDL功能,失功能高密度脂蛋白(dysfunctional high-density lipoproteins, dHDL)假说逐渐被接受。随着基因测序和大数据理论的发展,更深入地研究HDL会给心血管领域带来新的曙光。
Normal high density lipoprotein(HDL) has a protective effect on the cardiovascular system. However, the relationship between HDL cholesterol(HDL-C) and cardiovascular disease becomes more and more complicated, especially in studies of HDL metabolism-related gene mutation population and after the failure of pharmaceutical research on how to raise HDL cholesterol. The functions of HDL, including eliciting reverse cholesterol transport(RCT), anti-oxidant, anti-inflammatory, promoting angiogenesis, will lose in disease status and even turn harmful. The core of research was transferred from HDL-C to HDL's function, and the hypothesis of dysfunctional HDL(dHDL) was gradually accepted. With the development of gene sequencing and big data theory, further research of HDL will bring new dawn to cardiovascular field.
Normal high density lipoprotein(HDL) has a protective effect on the cardiovascular system. However, the relationship between HDL cholesterol(HDL-C) and cardiovascular disease becomes more and more complicated, especially in studies of HDL metabolism-related gene mutation population and after the failure of pharmaceutical research on how to raise HDL cholesterol. The functions of HDL, including eliciting reverse cholesterol transport(RCT), anti-oxidant, anti-inflammatory, promoting angiogenesis, will lose in disease status and even turn harmful. The core of research was transferred from HDL-C to HDL's function, and the hypothesis of dysfunctional HDL(dHDL) was gradually accepted. With the development of gene sequencing and big data theory, further research of HDL will bring new dawn to cardiovascular field.
引文
[1]Vickers KC, Palmisano BT, Shoucri BM, et al. MicroRNAs are transported in plasma and delivered to recipient cells by highdensity lipoproteins. Nat Cell Biol, 2011, 13(4):423-433.
[2]Rohatgi A, Khera A, Berry JD, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med,2014,371(25):2383-2393.
[3]Wilson PW, Abbott RD, Castelli WP. High density lipoprotein cholesterol and mortality. The Framingham Heart Study.Arteriosclerosis, 1988, 8(6):737-741.
[4]杨阳,张海波,蒋立新.升高高密度脂蛋白胆固醇药物的相关研究进展.中国分子心脏病学杂志,2010, 10(6):374-377.
[5]Khera AV, Patel PJ, Reilly MP, et al. The addition of niacin to statin therapy improves high-density lipoprotein cholesterol levels but not metrics of functionality. J Am Coll Cardiol, 2013,62(20):1909-1910.
[6]Di Bartolo B, Takata K, Duong M, et al. CETP Inhibition in CVD Prevention:an Actual Appraisal. Curr Cardiol Rep, 2016,18(5):43.
[7]Millwood IY, Bennett DA, Holmes MV, et al. Association of CETP Gene Variants With Risk for Vascular and Nonvascular Diseases Among Chinese Adults. JAMA Cardiol, 2018, 3(1):34-43.
[8]Wilkins JT,Ning H, Stone NJ, et al. Coronary heart disease risks associated with high levels of HDL cholesterol. J Am Heart Assoc, 2014, 3(2):e000519.
[9]Bowe B, Xie Y, Xian H, et al. High Density Lipoprotein Cholesterol and the Risk of All-Cause Mortality among U.S.Veterans. Clin J Am Soc Nephrol, 2016, 11(10):1784-1793.
[10]Ding D, Li X, Qiu J, et al. Serum lipids, apolipoproteins, and mortality among coronary artery disease patients. Biomed Res Int, 2014, 2014:709756.
[11]Hamer M, O'Donovan G, Stamatakis E. High-Density Lipoprotein Cholesterol and Mortality:Too Much of a Good Thing? Arterioscler Thromb Vasc Biol, 2018, 38(3):669-672.
[12]Van Lenten BJ, Hama SY, de Beer FC, et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response.Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest, 1995, 96(6):2758-2767.
[13]Ansell BJ, Navab M,Hama S,et al.Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation, 2003, 108(22):2751-2756.
[14]Sorrentino SA, Besler C, Rohrer L, et al. Endothelialvasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy. Circulation, 2010, 121(1):110-122.
[15]Riwanto M, Rohrer L, Roschitzki B, et al. Altered activation of endothelial anti-and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease:role of high-density lipoprotein-proteome remodeling. Circulation,2013, 127(8):891-904.
[16]Dullaart RP, Annema W, Tio RA, et al. The HDL antiinflammatory function is impaired in myocardial infarction and may predict new cardiac events independent of HDL cholesterol.Clin Chim Acta, 2014, 433:34-38.
[17]Annema W, Willemsen HM, de Boer JF, et al. HDL function is impaired in acute myocardial infarction independent of plasma HDL cholesterol levels. J Clin Lipidol, 2016, 10(6):1318-1328.
[18]Delbosc S, Diallo D, Dejouvencel T, et al. Impaired high-density lipoprotein anti-oxidant capacity in human abdominal aortic aneurysm. Cardiovasc Res, 2013, 100(2):307-315.
[19]Chang FJ, Yuan HY, Hu XX, et al. High density lipoprotein from patients with valvular heart disease uncouples endothelial nitric oxide synthase. J Mol Cell Cardiol, 2014, 74:209-219.
[20]Nicholls SJ, Ruotolo G,Brewer HB, et al. Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib. J Am Coll Cardiol, 2015, 66(20):2201-2210.
[21]Turner S, Voogt J, Davidson M, et al. Measurement of reverse cholesterol transport pathways in humans:in vivo rates of free cholesterol efflux, esterification, and excretion. J Am Heart Assoc, 2012, 1(4):e001826.
[22]Tall AR, Blum CB, Forester GP, et al. Changes in the distribution and composition of plasma high density lipoproteins after ingestion of fat. J Biol Chem, 1982, 257(1):198-207.
[23]Marz W, Kleber ME, Scharnagl H, et al. HDL cholesterol:reappraisal of its clinical relevance. Clin Res Cardiol, 2017. 106(9):663-675.
[24]Tardif JC, Rhainds D, Rheaume E, et al. CETP:Pharmacogenomics-Based Response to the CETP Inhibitor Dalcetrapib. Arterioscler Thromb Vase Biol, 2017, 37(3):396-400.
[2]Rohatgi A, Khera A, Berry JD, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med,2014,371(25):2383-2393.
[3]Wilson PW, Abbott RD, Castelli WP. High density lipoprotein cholesterol and mortality. The Framingham Heart Study.Arteriosclerosis, 1988, 8(6):737-741.
[4]杨阳,张海波,蒋立新.升高高密度脂蛋白胆固醇药物的相关研究进展.中国分子心脏病学杂志,2010, 10(6):374-377.
[5]Khera AV, Patel PJ, Reilly MP, et al. The addition of niacin to statin therapy improves high-density lipoprotein cholesterol levels but not metrics of functionality. J Am Coll Cardiol, 2013,62(20):1909-1910.
[6]Di Bartolo B, Takata K, Duong M, et al. CETP Inhibition in CVD Prevention:an Actual Appraisal. Curr Cardiol Rep, 2016,18(5):43.
[7]Millwood IY, Bennett DA, Holmes MV, et al. Association of CETP Gene Variants With Risk for Vascular and Nonvascular Diseases Among Chinese Adults. JAMA Cardiol, 2018, 3(1):34-43.
[8]Wilkins JT,Ning H, Stone NJ, et al. Coronary heart disease risks associated with high levels of HDL cholesterol. J Am Heart Assoc, 2014, 3(2):e000519.
[9]Bowe B, Xie Y, Xian H, et al. High Density Lipoprotein Cholesterol and the Risk of All-Cause Mortality among U.S.Veterans. Clin J Am Soc Nephrol, 2016, 11(10):1784-1793.
[10]Ding D, Li X, Qiu J, et al. Serum lipids, apolipoproteins, and mortality among coronary artery disease patients. Biomed Res Int, 2014, 2014:709756.
[11]Hamer M, O'Donovan G, Stamatakis E. High-Density Lipoprotein Cholesterol and Mortality:Too Much of a Good Thing? Arterioscler Thromb Vasc Biol, 2018, 38(3):669-672.
[12]Van Lenten BJ, Hama SY, de Beer FC, et al. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response.Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Invest, 1995, 96(6):2758-2767.
[13]Ansell BJ, Navab M,Hama S,et al.Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation, 2003, 108(22):2751-2756.
[14]Sorrentino SA, Besler C, Rohrer L, et al. Endothelialvasoprotective effects of high-density lipoprotein are impaired in patients with type 2 diabetes mellitus but are improved after extended-release niacin therapy. Circulation, 2010, 121(1):110-122.
[15]Riwanto M, Rohrer L, Roschitzki B, et al. Altered activation of endothelial anti-and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease:role of high-density lipoprotein-proteome remodeling. Circulation,2013, 127(8):891-904.
[16]Dullaart RP, Annema W, Tio RA, et al. The HDL antiinflammatory function is impaired in myocardial infarction and may predict new cardiac events independent of HDL cholesterol.Clin Chim Acta, 2014, 433:34-38.
[17]Annema W, Willemsen HM, de Boer JF, et al. HDL function is impaired in acute myocardial infarction independent of plasma HDL cholesterol levels. J Clin Lipidol, 2016, 10(6):1318-1328.
[18]Delbosc S, Diallo D, Dejouvencel T, et al. Impaired high-density lipoprotein anti-oxidant capacity in human abdominal aortic aneurysm. Cardiovasc Res, 2013, 100(2):307-315.
[19]Chang FJ, Yuan HY, Hu XX, et al. High density lipoprotein from patients with valvular heart disease uncouples endothelial nitric oxide synthase. J Mol Cell Cardiol, 2014, 74:209-219.
[20]Nicholls SJ, Ruotolo G,Brewer HB, et al. Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib. J Am Coll Cardiol, 2015, 66(20):2201-2210.
[21]Turner S, Voogt J, Davidson M, et al. Measurement of reverse cholesterol transport pathways in humans:in vivo rates of free cholesterol efflux, esterification, and excretion. J Am Heart Assoc, 2012, 1(4):e001826.
[22]Tall AR, Blum CB, Forester GP, et al. Changes in the distribution and composition of plasma high density lipoproteins after ingestion of fat. J Biol Chem, 1982, 257(1):198-207.
[23]Marz W, Kleber ME, Scharnagl H, et al. HDL cholesterol:reappraisal of its clinical relevance. Clin Res Cardiol, 2017. 106(9):663-675.
[24]Tardif JC, Rhainds D, Rheaume E, et al. CETP:Pharmacogenomics-Based Response to the CETP Inhibitor Dalcetrapib. Arterioscler Thromb Vase Biol, 2017, 37(3):396-400.
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