Andrea Frustaci1, Fabiola Ciccosanti2, Cristina Chimenti1, Roberta Nardacci2, Marco Corazzari3, Romina Verardo2, Giuseppe Ippolito2, Nicola Petrosillo2, Gian Maria Fimia4, Mauro Piacentini3. 1. Department of Cardiovascular, Nefrologic, Anestesiologic and Geriatric Sciences, La Sapienza University, Italy; National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Rome, Italy. 2. National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Rome, Italy. 3. National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Rome, Italy; Department of Biology, University of Rome 'Tor Vergata', Rome, Italy. 4. National Institute for Infectious Diseases IRCCS 'L. Spallanzani', Rome, Italy; Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce 73100, Italy.
Abstract
BACKGROUND: Diabetic cardiomyopathy (DbCM) is indistinguishable from idiopathic dilated cardiomyopathy (IDCM) as specific histological and/or biochemical markers are unavailable. METHODS AND RESULTS: Comparative histology, electron microscopy, morphometry for cell volume composition and myocardial fibrosis, reactive oxygen species (ROS), polymerase chain reaction for cardiotropic viruses, immunohistochemistry for nitrotyrosine, inducible nitric oxide synthase (iNOS), 8-hydroxydeoxyguanosine (8-OH-dG) and proteomics have been evaluated in endomyocardial biopsies from 9 patients (pts) (5 male and 4 female, mean age 61 ± 13 years) with DbCM (left ventricular end-diastolic diameter 65 ± 2.3mm; ejection fraction 27 ± 6) and type 2 diabetes mellitus and 9 pts with IDCM (mean age 60 ± 9 years) matched for sex, age and severity of left ventricular (LV) dysfunction. Controls were surgical biopsies from 9 pts with mitral stenosis and normal LV dimensions and function. No qualitative morphological changes were observed between DbCM and IDCM although mitochondrial damage and myofibrillolysis appeared more pronounced in DbCM. ROS were 5 times higher in DbCM than in IDCM and controls and were associated with higher expression of cytoplasm iNOS and nitrotyrosine and nuclear 8-OH-dG. Apoptosis was 14 times higher in DbCM than in IDCM and 41 times higher than in controls. Proteomic profile showed in DbCM a reduced expression of proteins related to beta-oxidation and detoxification pathway. CONCLUSIONS: DbCM is a distinctive ROS-mediated disorder with oxidative damage of myocyte's structural proteins and DNA causing cell dysfunction and death. Reduced expression of beta-oxidation proteins suggests a decline of energy production and of mitochondrial function.
BACKGROUND:Diabetic cardiomyopathy (DbCM) is indistinguishable from idiopathic dilated cardiomyopathy (IDCM) as specific histological and/or biochemical markers are unavailable. METHODS AND RESULTS: Comparative histology, electron microscopy, morphometry for cell volume composition and myocardial fibrosis, reactive oxygen species (ROS), polymerase chain reaction for cardiotropic viruses, immunohistochemistry for nitrotyrosine, inducible nitric oxide synthase (iNOS), 8-hydroxydeoxyguanosine (8-OH-dG) and proteomics have been evaluated in endomyocardial biopsies from 9 patients (pts) (5 male and 4 female, mean age 61 ± 13 years) with DbCM (left ventricular end-diastolic diameter 65 ± 2.3mm; ejection fraction 27 ± 6) and type 2 diabetes mellitus and 9 pts with IDCM (mean age 60 ± 9 years) matched for sex, age and severity of left ventricular (LV) dysfunction. Controls were surgical biopsies from 9 pts with mitral stenosis and normal LV dimensions and function. No qualitative morphological changes were observed between DbCM and IDCM although mitochondrial damage and myofibrillolysis appeared more pronounced in DbCM. ROS were 5 times higher in DbCM than in IDCM and controls and were associated with higher expression of cytoplasm iNOS and nitrotyrosine and nuclear 8-OH-dG. Apoptosis was 14 times higher in DbCM than in IDCM and 41 times higher than in controls. Proteomic profile showed in DbCM a reduced expression of proteins related to beta-oxidation and detoxification pathway. CONCLUSIONS: DbCM is a distinctive ROS-mediated disorder with oxidative damage of myocyte's structural proteins and DNA causing cell dysfunction and death. Reduced expression of beta-oxidation proteins suggests a decline of energy production and of mitochondrial function.
Authors: Bradley S Lander; Yanling Zhao; Kohei Hasegawa; Mathew S Maurer; Albree Tower-Rader; Michael A Fifer; Muredach P Reilly; Yuichi J Shimada Journal: Front Cardiovasc Med Date: 2022-06-17
Authors: Jerzy Pacholewicz; Michał Zakliczyński; Jerzy Nożyński; Paweł Nadziakiewicz; Michał Zembala; Marian Zembala Journal: Kardiochir Torakochirurgia Pol Date: 2019-06-28