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Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels

BACKGROUND: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased...

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Autores principales: 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 Jane, Kelly, Darren J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506639/
https://www.ncbi.nlm.nih.gov/pubmed/23189164
http://dx.doi.org/10.1371/journal.pone.0049813
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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 Jane
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 Jane
Kelly, Darren J.
author_sort Campbell, Duncan J.
collection PubMed
description BACKGROUND: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. METHODS: We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. RESULTS: The patients were aged 43–78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e’ (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e’ was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e’ (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e’ remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate. CONCLUSIONS: Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.
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spelling pubmed-35066392012-11-27 Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels 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 Jane Kelly, Darren J. PLoS One Research Article BACKGROUND: Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) N(ε)-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. METHODS: We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. RESULTS: The patients were aged 43–78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e’ (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e’ was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e’ (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e’ remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate. CONCLUSIONS: Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels. Public Library of Science 2012-11-26 /pmc/articles/PMC3506639/ /pubmed/23189164 http://dx.doi.org/10.1371/journal.pone.0049813 Text en © 2012 Campbell et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
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 Jane
Kelly, Darren J.
Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels
title Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels
title_full Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels
title_fullStr Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels
title_full_unstemmed Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels
title_short Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels
title_sort diastolic dysfunction of aging is independent of myocardial structure but associated with plasma advanced glycation end-product levels
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506639/
https://www.ncbi.nlm.nih.gov/pubmed/23189164
http://dx.doi.org/10.1371/journal.pone.0049813
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