Histological and proteomic profile of diabetic versus non-diabetic dilated cardiomyopathy

Research output: Contribution to journalArticle

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 ± 2.3 mm; 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.

Original languageEnglish
Pages (from-to)282-289
Number of pages8
JournalInternational Journal of Cardiology
Volume203
DOIs
Publication statusPublished - Jan 15 2016

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Diabetic Cardiomyopathies
Dilated Cardiomyopathy
Proteomics
Reactive Oxygen Species
Nitric Oxide Synthase Type II
Comparative Histology
Biopsy
Proteins
Mitral Valve Stenosis
Left Ventricular Dysfunction
Cell Size
Left Ventricular Function
Muscle Cells
Type 2 Diabetes Mellitus
Electron Microscopy
Cytoplasm
Fibrosis
Cell Death
Biomarkers
Immunohistochemistry

Keywords

  • Cardiomyopathy
  • Diabetes
  • Oxidative damage
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{2cf19dd2ce974b3b9b15c248c09de2a1,
title = "Histological and proteomic profile of diabetic versus non-diabetic dilated cardiomyopathy",
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 ± 2.3 mm; 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.",
keywords = "Cardiomyopathy, Diabetes, Oxidative damage, Reactive oxygen species",
author = "Andrea Frustaci and Fabiola Ciccosanti and Cristina Chimenti and Roberta Nardacci and Marco Corazzari and Romina Verardo and Giuseppe Ippolito and Nicola Petrosillo and Fimia, {Gian Maria} and Mauro Piacentini",
year = "2016",
month = "1",
day = "15",
doi = "10.1016/j.ijcard.2015.10.119",
language = "English",
volume = "203",
pages = "282--289",
journal = "International Journal of Cardiology",
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publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Histological and proteomic profile of diabetic versus non-diabetic dilated cardiomyopathy

AU - Frustaci, Andrea

AU - Ciccosanti, Fabiola

AU - Chimenti, Cristina

AU - Nardacci, Roberta

AU - Corazzari, Marco

AU - Verardo, Romina

AU - Ippolito, Giuseppe

AU - Petrosillo, Nicola

AU - Fimia, Gian Maria

AU - Piacentini, Mauro

PY - 2016/1/15

Y1 - 2016/1/15

N2 - 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 ± 2.3 mm; 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.

AB - 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 ± 2.3 mm; 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.

KW - Cardiomyopathy

KW - Diabetes

KW - Oxidative damage

KW - Reactive oxygen species

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U2 - 10.1016/j.ijcard.2015.10.119

DO - 10.1016/j.ijcard.2015.10.119

M3 - Article

AN - SCOPUS:84952683689

VL - 203

SP - 282

EP - 289

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -