Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress

Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced left ventricular hypertrophy (L...

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Main Authors: Michel eKINDO, Sebastien eGERELLI, Jamal eBOUITBIR, Anne-Laure eCHARLES, Joffrey eZOLL, Tam eHOANG MINH, Laurent eMONASSIER, Fabrice eFAVRET, Francois ePIQUARD, Bernard eGENY
Format: Article
Language:English
Published: Frontiers Media S.A. 2012-08-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00332/full
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author Michel eKINDO
Sebastien eGERELLI
Jamal eBOUITBIR
Anne-Laure eCHARLES
Joffrey eZOLL
Tam eHOANG MINH
Laurent eMONASSIER
Fabrice eFAVRET
Francois ePIQUARD
Bernard eGENY
author_facet Michel eKINDO
Sebastien eGERELLI
Jamal eBOUITBIR
Anne-Laure eCHARLES
Joffrey eZOLL
Tam eHOANG MINH
Laurent eMONASSIER
Fabrice eFAVRET
Francois ePIQUARD
Bernard eGENY
author_sort Michel eKINDO
collection DOAJ
description Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced left ventricular hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n=10 for each group). Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilised fibres, Amplex Red fluorescence and citrate synthase activity.Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P<0.01) and complex IV activity (-57.4%, P<0.05). Mitochondrial hydrogen peroxide (H2O2) production was similar in both LV layers.Aortic banding induced mild LVH (+31.7% LV mass), associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%), increased mitochondrial H2O2 production (+86.9 and +73.1%), free radical leak (+27.2% and +36.3%) and citrate synthase activity (+27.2% and +36.3%) in Endo and Epi, respectively.Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs –12.2%; P=0.02). Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.
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spelling doaj.art-30dfc5c88b1046bd8769e6ec7bd7471c2022-12-22T01:47:00ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-08-01310.3389/fphys.2012.0033227733Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stressMichel eKINDO0Sebastien eGERELLI1Jamal eBOUITBIR2Anne-Laure eCHARLES3Joffrey eZOLL4Tam eHOANG MINH5Laurent eMONASSIER6Fabrice eFAVRET7Francois ePIQUARD8Bernard eGENY9CHRU Strasbourg et Equipe d’Accueil 3072, Université de StrasbourgCHRU Strasbourg et Equipe d’Accueil 3072, Université de StrasbourgCHRU Strasbourg et EA 3072, Université de StrasbourgCHRU Strasbourg et EA 3072, Université de StrasbourgCHRU Strasbourg et EA 3072, Université de StrasbourgCHRU Strasbourg et Equipe d’Accueil 3072, Université de StrasbourgUniversité de StrasbourgUniversité de StrasbourgCHRU Strasbourg et EA 3072, Université de StrasbourgCHRU Strasbourg et EA 3072, Université de StrasbourgObjective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo) but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi) and whether pressure overload-induced left ventricular hypertrophy (LVH) might modulate transmural gradients through increased reactive oxygen species (ROS) production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n=10 for each group). Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilised fibres, Amplex Red fluorescence and citrate synthase activity.Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P<0.01) and complex IV activity (-57.4%, P<0.05). Mitochondrial hydrogen peroxide (H2O2) production was similar in both LV layers.Aortic banding induced mild LVH (+31.7% LV mass), associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%), increased mitochondrial H2O2 production (+86.9 and +73.1%), free radical leak (+27.2% and +36.3%) and citrate synthase activity (+27.2% and +36.3%) in Endo and Epi, respectively.Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs –12.2%; P=0.02). Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00332/fullHeartHypertrophyMitochondriaAortic bandingOxydative stressPressure overload
spellingShingle Michel eKINDO
Sebastien eGERELLI
Jamal eBOUITBIR
Anne-Laure eCHARLES
Joffrey eZOLL
Tam eHOANG MINH
Laurent eMONASSIER
Fabrice eFAVRET
Francois ePIQUARD
Bernard eGENY
Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress
Frontiers in Physiology
Heart
Hypertrophy
Mitochondria
Aortic banding
Oxydative stress
Pressure overload
title Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress
title_full Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress
title_fullStr Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress
title_full_unstemmed Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress
title_short Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress
title_sort pressure overload induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress
topic Heart
Hypertrophy
Mitochondria
Aortic banding
Oxydative stress
Pressure overload
url http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00332/full
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