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Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease
BACKGROUND: Type 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 adv...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182888/ https://www.ncbi.nlm.nih.gov/pubmed/21929744 http://dx.doi.org/10.1186/1475-2840-10-80 |
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author | Campbell, Duncan J Somaratne, Jithendra B Jenkins, Alicia J Prior, David L Yii, Michael Kenny, James F Newcomb, Andrew E Schalkwijk, Casper G Black, Mary J Kelly, Darren J |
author_facet | Campbell, Duncan J Somaratne, Jithendra B Jenkins, Alicia J Prior, David L Yii, Michael Kenny, James F Newcomb, Andrew E Schalkwijk, Casper G Black, Mary J Kelly, Darren J |
author_sort | Campbell, Duncan J |
collection | PubMed |
description | BACKGROUND: Type 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. METHODS: We 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. RESULTS: All 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. CONCLUSIONS: Impaired 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. |
format | Online Article Text |
id | pubmed-3182888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31828882011-09-30 Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease Campbell, Duncan J Somaratne, Jithendra B Jenkins, Alicia J Prior, David L Yii, Michael Kenny, James F Newcomb, Andrew E Schalkwijk, Casper G Black, Mary J Kelly, Darren J Cardiovasc Diabetol Original Investigation BACKGROUND: Type 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. METHODS: We 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. RESULTS: All 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. CONCLUSIONS: Impaired 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. BioMed Central 2011-09-19 /pmc/articles/PMC3182888/ /pubmed/21929744 http://dx.doi.org/10.1186/1475-2840-10-80 Text en Copyright ©2011 Campbell et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Investigation Campbell, Duncan J Somaratne, Jithendra B Jenkins, Alicia J Prior, David L Yii, Michael Kenny, James F Newcomb, Andrew E Schalkwijk, Casper G Black, Mary J Kelly, Darren J Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease |
title | Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease |
title_full | Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease |
title_fullStr | Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease |
title_full_unstemmed | Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease |
title_short | Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease |
title_sort | impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182888/ https://www.ncbi.nlm.nih.gov/pubmed/21929744 http://dx.doi.org/10.1186/1475-2840-10-80 |
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