糖尿病心肌病发病机制的研究进展

摘要/Abstract

摘要： 糖尿病威胁人类的健康日益突出。高血糖引起的心血管并发症涉及到心肌病变和血管病变。而糖尿病引起的糖尿病心肌病发病机制是由多因素所致,糖尿病通过各种心肌细胞器结构的改变(线粒体、内质网等)、信号途径、酶学及基因学的变化和炎症因子等病理机制,导致心脏纤维化、心肌肥厚、心脏扩大、心力衰竭和心律失常。本综述详细阐述糖尿病心肌病发病机制的研究进展。

关键词: 糖尿病, 心肌病, 发病机制, 心肌病/糖尿病性, 高血糖

Abstract: Diabetes mellitus has emerged as a major threat to worldwide health.Cardiovascular complications associated with hyperglycemia include cardiomyopathy and vasculopathy.The pathophysiology of diabetic cardiomyopathy is likely multifactorial, with experimental evidence pointing to involvement of the structural changers of cardiac muscle cell organelle(such as mitochondrion,endoplasmic reticulum), signal pathway, the variations of enzymology and gene, and inflammatory factors. These molecular and cellular events culminate in the development of cardiac fibrosis, hypertrophy, cardiac dilatation, heart failure and arrhythmia leading to cardiac dysfunction and enhanced injury. This review article expounds detailed research progress of pathogenesis of diabetic cardiomyopathy.

Key words: Diabetes mellitus, Cardiomyopathy, Pathogenesis, Cardiomyopathy/diabetic, Hyperglycemia

中图分类号:

R542.2

潘大彬, 汪旻晖, 曹蘅. 糖尿病心肌病发病机制的研究进展[J]. 中国临床药理学与治疗学, 2013, 18(7): 831-836.

PAN Da-bin, WANG Min-hui, CAO Heng. Research progress of pathogenesis of diabetic cardiomyopathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(7): 831-836.

参考文献

[1] Falcao PI, Leite-Moreira AF. Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment[J]. Heart Fail Rev, 2012, 17(3): 325- 344.
[2] Cioffi G, Faggiano P, Lucci D, et al. Inappropriately high left ventricular mass in patients with type 2 diabetes mellitus and no overt cardiac disease. The DYDA study[J]. J Hypertens ,2011, 29(10): 1994-2003.
[3] Shah AM, Shin SH, Takeuchi M, et al. Left ventricular systolic and diastolic function, remodelling, and clinical outcomes among patients with diabetes following myocardial infarction and the influence of direct renin inhibition with aliskiren[J]. Eur J Heart Fail, 2012, 14(2): 185-192.
[4] Nagy A, Cserep Z. Link between diabetes and diastolic dysfunction and the diagnosis role of echocardiography[J]. Orv Hetil, 2009, 150(45): 2060-2067.
[5] Santos CD, Souza AM, Pereira RM, et al. Assessment of diastolic function in children and adolescents with type 1 diabetes mellitus - are there early signs of diabetic cardiomyopathy [J]? Arg Bras Endocrinol Metabol, 2012, 56(4): 226-232.
[6] Dinh W, Füth R, Lankisch M, et al. Cardiovascular autonomic neuropathy contributes to left ventricular diastolic dysfunction in subjects with Type 2 diabetes and impaired glucose tolerance undergoing coronary angiography[J]. Diabet Med, 2011, 28(3):311-318.
[7] Kim DH, Kim YJ, Kim HK, et al. Usefulness of mitral annulus velocity for the early detection of left ventricular dysfunction in a rat model of diabetic cardiomyopathy[J]. J Cardiovasc Ultrasound, 2010, 18(1): 6-11.
[8] Hung KC, Lee CH, Chen CC, et al. Advanced left ventricular diastolic dysfunction in uremic patients with type 2 diabetes on maintenance hemodialysis[J]. Circ J, 2012, 76(10): 2380-2385.
[9] Wu WH, Sun ZJ, Li Q, et al. Influence of the glucose-lowering rate on left ventricular function in patient with type 2 diabetes and coronary heart disease[J]. J Diabetes Complications, 2012, 26(2): 83-88.
[10] Giannetta E, Isidori AM, Calea N, et al. Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy[J]. Circulation, 2012,125(19):2323-2333.
[11] Piya MK, Shivu GN, Tahrani A, et al. Abnormal left ventricular torsion and cardiac autonomic dysfunction in subjects with type 1 diabetes mellitus[J]. Metabolism, 2011,60(8): 1115-1121.
[12] Winhofer Y, Krssak M, Jankovic D, et al. Short-Term Hyperinsulinemia and Hyperglycemia Increase Myocardial Lipid Content in Normal Subjects[J]. Diabetes, 2012,61(5):1210-1216.
[13] Busche MN, Walsh MC, McMullen ME, et al. Mannose-binding lectin plays a critical role in myocardial ischaemia and reperfusion injury in a mouse model of diabetes [J]. Diabetologia, 2008,51(8): 1544-1551.
[14] Law B, Fowlkes V, Goldsmith JG, et al. Diabetes-induced alterationas in the extracellular matrix and their impact on myocardial function[J]. Microsc Microanal, 2012,18(1):22-34.
[15] Costas CT, Ioannis IB, Alexandros AK, et al. The role of matrix metalloproteinases in diabetes mellitus[J]. Curr Top Med Chem, 2012, 12(10): 1159-1165.
[16] Widyantoro B, Emoto N, Nakayama K, et al. Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts through stimulation of endothelial-to-mesenchymal transition[J]. Circulation, 2010, 121(22): 2407-2418.
[17] Kumar R, Qian CY, Candice MT, et al. Intracardiac intracellular angiotension system in diabetes[J]. Am J Physiol Regul Integr Comp Physiol, 2012, 302(5): R510-517.
[18] Mishra PK, Tyagi N, Sen U, et al. Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol[J]. Cardiovasc Diabeto,2010, 9:49-61.
[19] Mishra PK, Givvimani S, Metreveli N, et al. Attenuation of beta2-adrenergic receptors and homocysteine metabolic enzymes cause diabetic cardiomyopathy[J]. Biochem Biophys Res Commun, 2010, 401(2):175-181.
[20] Campbell DJ, Somaratne JB, Jenkins AJ, et al. Impact of type 2 diabetes and the metabolic ayndrome on myocardial structure and microvasculature of men with coronary artery disease[J]. Cardiovasc Diabetol, 2011, 10: 80-93.
[21] Hillis GS, Woodward M, Rodgers A, et al. Resting heart rate and the risk of death and cardiovascular complications in patients with type 2 diabetes mellitus[J]. Diabetologia, 2012, 55(5): 1283-1290.
[22] Fleischer J, Charles M, Tarnow L, et al. Paper electrocardiograph strips may contain overlooked clinical information in screen-detected type 2 diabetes patients[J]. J Diabetes Sci Technol, 2012,6(1): 74-80.
[23] Schannwell CM, Schneppenheim M, Perings S, et al. Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy[J]. Cardiology, 2002, 98(1/2): 33-39.
[24] Wang Y, Xuan YL, Hu HS, et al. Risk of ventricular arrhythmias after myocardial infraction with diabetes associated with sympathetic neural remodeling in rabbits[J]. Cardiology, 2012, 121(1):1-9.
[25] Jankyova S, Kmecova J, Cernecka H, et al. Glucose and blood pressure lowering effects of Pycnogenol(®) are inefficient to prevent prolongation of QT interval in experimental diabetic cardiomyopathy[J]. Pathol Res Pract, 2012, 208(8): 452-457.
[26] Nakamura H, Matoba S, Iwai-Kanai E, et al. p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation[J]. Circ Heart Fail, 2012, 5(1): 106-115.
[27] Lakshmanan AP, Harima M, Sukumaran V, et al. Modulation of AT-1R/AMPK-MAPK cascade plays crucial role for the pathogenesis of diabetic cardiomyopathy in transgenic type 2 diabetic (Spontaneous Diabetic Torii) rats[J]. Biochem Pharmacol, 2012,83(5):653-660.
[28] Zhang YC, Mou YL, Xie YY. Research progress in relations between rennin angiotensin system and diabetic cardiomyopathy[J]. Progress in Physiological Sciences, 2011,42(4): 269-275.
[29] Gui C, Zhu L,Hu M, et al. Neuregulin-1/ErbB signaling is impaired in the rat model of diabetic cardiomyopathy[J]. Cardiovasc Pathol, 2012,21(5):414-420.
[30] Xu Q, Dalic A, Fang L, et al. Myocardial oxidative stress contributes to transgenic β2-adrenoceptor activation- induced cardiomyopathy and heart failure[J]. Br J Pharmacol, 2011, 162(5): 1012-1028.
[31] Pavlov VI, La Bonte LR, Baldwin WM, et al. Absence of mannose-binding lectin prevents hyperglycemic cardiovascular complications[J]. Am J Pathol, 2012, 180(1): 104-112.
[32] Tang MX, Zhou FH, Zhang W, et al. The role of thrombospondin-1-mediated TGF-β1 on collagen type Ⅲ synthesis induced by high glucose[J]. Mol Cell Biochem, 2011, 346(1/2): 49-56.
[33] Lorenzo O, Picatoste B, Ares-Carrasco S, et al. Potential role of nuclear factor κB in diabetic cardiomypathy[J]. Mediators Inflamm, 2011, Article ID: 652097, doi: 10.1155/2011/652097.
[34] Kohda Y, Kanematsu M, Kono T, et al. Protein O-Glycosylation induces collagen expression and contributes to diabetic cardiomyopathy in rat cardiac fibroblasts[J]. J Pharmacol Sci, 2011, 111(4): 446-450.
[35] Sheikh AQ, Hurley JR, Huang W, et al. Diabetes alters intracellular calcium transients in cardiac endothelial cells[J]. PLoS One,2012, 7(5):e368-340.
[36] Kranstuber AL, Del Rio C, Biesiadecki BJ, et al. Advanced glycation end product crosslink breaker attenuates diabetes induced cardiac dysfunction by improving sarcoplasmic reticulum calcium handling[J]. Front Physiol, 2012, 3: 292. dio:10.3389/fphys.2012.00292.
[37] Bai SZ, Sun J, Wu H, et al. Decrease in calcium-sensing receptor in the progress of diabetic cardiomyopathy[J]. Diabetes Res Clin Pract, 2012, 95(3): 378-385.
[38] Zhang YM, Babcock SA, Hu N, et al. Mitochondrial aldehyde dehydrogenase (ALDH2) protects against streptozotocin-induced diabetic cardiomyopathy: role of GSK3β and mitochondrial function[J]. BMC Med, 2012, 10: 40, doi: 10.1186/1741-7015-10-40.
[39] Zhou C, La Bonte LR, Pavlov VI, et al. Murine hyperglycemic vasculopathy and cardiomyopathy: whole-genome gene expression analysis predicts cellular targets and regulatory networks influenced by mannose binding lectin[J]. Front Immunol, 2012, 3(15): 1-9.
[40] Rosca MG, Hoppel CL. Mitochondria in heart failure [J]. Cardiovasc Res, 2010, 88(1): 40-50.
[41] Bugger H, Abel ED. Mitochondria in the diabetic heart[J]. Cardiovas Res, 2010, 88(2): 229-240.
[42] Bertrand L, Horman S, Beauloye C, et al. Insulinsignalling in the heart[J]. Cardiovasc Res, 2008, 79(2): 238-248.
[43] Sloan RC, Moukdar F, Frasier CR, et al. Mitochondrial permeability transition in the diabetic heart: contributions of thiol redox state and mitochondrial calcium to augmented reperfusion injury[J]. J Mol Cell Cardiol, 2012, 52(5): 1009-1018.
[44] Xu JC, Zhou Q, Xu W, et al. Endoplasmic Reticulum Stress and Diabetic Cardiomyopathy[J]. Exp Diabetes Res, 2012, Article ID 827971, dio:10.1155/2012/927971
[45] Nano Y, Anzai T, Kaneko H, et al. Overexpression of human C-reactive protein exacerbates left ventricular remodeling in diabetic cardiomyopathy[J]. Circ J, 2011, 75(7): 1717-1727.
[46] Soman S, Manju CS, Rauf AA, et al. Role of cardiac isoform of alpha-2 macroglobulin in diabetic myocardium[J]. Mol Cell Biochem, 2011, 350(1/2): 229-235.
[47] Aksakal E, Akaras N, Kurt M, et al. The role of oxidative stress in diabetic cardiomyopathy: an experimental study[J]. Eur Rev Med Pharmacol Sci, 2011, 15(11):1241-1246.
[48] Feng B, Chen S, Chiu J, et al. Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level[J]. Am J Physiol Endocrinol Metab, 2008, 294(6): E1119-1126.