Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

Cardiovascular Diabetology

Original Investigation

Mary J Black¹  Jithendra B Somaratne²  James F Kenny³  Casper G Schalkwijk⁴  Alicia J Jenkins⁵  Darren J Kelly⁵  Duncan J Campbell⁶  David L Prior⁷  Andrew E Newcomb⁸  Michael Yii⁸ 

[1] Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia;Department of Cardiology, St. Vincent's Health, Fitzroy, Australia;Department of Cardiothoracic Surgery, St. Vincent's Health, Fitzroy, Australia;Department of Internal Medicine, University of Maastricht, Maastricht, The Netherlands;Department of Medicine, University of Melbourne, St. Vincent's Health, Fitzroy, Australia;Department of Molecular Cardiology, St. Vincent's Institute of Medical Research, Fitzroy, Australia;Department of Medicine, University of Melbourne, St. Vincent's Health, Fitzroy, Australia;Department of Molecular Cardiology, St. Vincent's Institute of Medical Research, Fitzroy, Australia;Department of Medicine, University of Melbourne, St. Vincent's Health, Fitzroy, Australia;Department of Cardiology, St. Vincent's Health, Fitzroy, Australia;Department of Surgery, University of Melbourne, St. Vincent's Health, Fitzroy, Australia;Department of Cardiothoracic Surgery, St. Vincent's Health, Fitzroy, Australia;

关键词: Diabetic cardiomyopathy;    type 2 diabetes;    metabolic syndrome;    fibrosis;    capillary length density;    advanced glycation end-products;   

DOI  :  10.1186/1475-2840-10-80

 received in 2011-07-17, accepted in 2011-09-19,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundType 2 diabetes and the metabolic syndrome are associated with impaired diastolic function and increased heart failure risk. Animal models and autopsy studies of diabetic patients implicate myocardial fibrosis, cardiomyocyte hypertrophy, altered myocardial microvascular structure and advanced glycation end-products (AGEs) in the pathogenesis of diabetic cardiomyopathy. We investigated whether type 2 diabetes and the metabolic syndrome are associated with altered myocardial structure, microvasculature, and expression of AGEs and receptor for AGEs (RAGE) in men with coronary artery disease.MethodsWe performed histological analysis of left ventricular biopsies from 13 control, 10 diabetic and 23 metabolic syndrome men undergoing coronary artery bypass graft surgery who did not have heart failure or atrial fibrillation, had not received loop diuretic therapy, and did not have evidence of previous myocardial infarction.ResultsAll three patient groups had similar extent of coronary artery disease and clinical characteristics, apart from differences in metabolic parameters. Diabetic and metabolic syndrome patients had higher pulmonary capillary wedge pressure than controls, and diabetic patients had reduced mitral diastolic peak velocity of the septal mitral annulus (E'), consistent with impaired diastolic function. Neither diabetic nor metabolic syndrome patients had increased myocardial interstitial fibrosis (picrosirius red), or increased immunostaining for collagen I and III, the AGE Nε-(carboxymethyl)lysine, or RAGE. Cardiomyocyte width, capillary length density, diffusion radius, and arteriolar dimensions did not differ between the three patient groups, whereas diabetic and metabolic syndrome patients had reduced perivascular fibrosis.ConclusionsImpaired diastolic function of type 2 diabetic and metabolic syndrome patients was not dependent on increased myocardial fibrosis, cardiomyocyte hypertrophy, alteration of the myocardial microvascular structure, or increased myocardial expression of Nε-(carboxymethyl)lysine or RAGE. These findings suggest that the increased myocardial fibrosis and AGE expression, cardiomyocyte hypertrophy, and altered microvasculature structure described in diabetic heart disease were a consequence, rather than an initiating cause, of cardiac dysfunction.

【 授权许可】

CC BY   
© Campbell et al; licensee BioMed Central Ltd. 2011