Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage

Background Aldehyde dehydrogenase‐2 (ALDH2), a mitochondrial enzyme, detoxifies reactive aldehydes such as 4‐hydroxy‐2‐nonenal (4HNE). A highly prevalent E487K mutation in ALDH2 (ALDH2*2) in East Asian people with intrinsic low ALDH2 activity is implicated in diabetic complications. 4HNE‐induced car...

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Autores principales:	Guodong Pan, Bipradas Roy, Suresh Selvaraj Palaniyandi
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	aldehyde dehydrogenase‐2 cardiac dysfunction coronary endothelial cells diabetic heart ischemia‐reperfusion injury Langendorff system Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/6d08815a1b214cd8b9cf068fc03d0cf9
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spelling	oai:doaj.org-article:6d08815a1b214cd8b9cf068fc03d0cf92021-11-23T11:36:35ZDiabetic Aldehyde Dehydrogenase 2 Mutant (ALDH22) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage10.1161/JAHA.121.0211402047-9980https://doaj.org/article/6d08815a1b214cd8b9cf068fc03d0cf92021-09-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.021140https://doaj.org/toc/2047-9980Background Aldehyde dehydrogenase‐2 (ALDH2), a mitochondrial enzyme, detoxifies reactive aldehydes such as 4‐hydroxy‐2‐nonenal (4HNE). A highly prevalent E487K mutation in ALDH2 (ALDH22) in East Asian people with intrinsic low ALDH2 activity is implicated in diabetic complications. 4HNE‐induced cardiomyocyte dysfunction was studied in diabetic cardiac damage; however, coronary endothelial cell (CEC) injury in myocardial ischemia‐reperfusion injury (IRI) in diabetic mice has not been studied. Therefore, we hypothesize that the lack of ALDH2 activity exacerbates 4HNE‐induced CEC dysfunction which leads to cardiac damage in ALDH22 mutant diabetic mice subjected to myocardial IRI. Methods and Results Three weeks after diabetes mellitus (DM) induction, hearts were subjected to IRI either in vivo via left anterior descending artery occlusion and release or ex vivo IRI by using the Langendorff system. The cardiac performance was assessed by conscious echocardiography in mice or by inserting a balloon catheter in the left ventricle in the ex vivo model. Just 3 weeks of DM led to an increase in cardiac 4HNE protein adducts and, cardiac dysfunction, and a decrease in the number of CECs along with reduced myocardial ALDH2 activity in ALDH22 mutant diabetic mice compared with their wild‐type counterparts. Systemic pretreatment with Alda‐1 (10 mg/kg per day), an activator of both ALDH2 and ALDH2*2, led to a reduction in myocardial infarct size and dysfunction, and coronary perfusion pressure upon cardiac IRI by increasing CEC population and coronary arteriole opening. Conclusions Low ALDH2 activity exacerbates 4HNE‐mediated CEC injury and thereby cardiac dysfunction in diabetic mouse hearts subjected to IRI, which can be reversed by ALDH2 activation.Guodong PanBipradas RoySuresh Selvaraj PalaniyandiWileyarticlealdehyde dehydrogenase‐2cardiac dysfunctioncoronary endothelial cellsdiabetic heartischemia‐reperfusion injuryLangendorff systemDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aldehyde dehydrogenase‐2 cardiac dysfunction coronary endothelial cells diabetic heart ischemia‐reperfusion injury Langendorff system Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	aldehyde dehydrogenase‐2 cardiac dysfunction coronary endothelial cells diabetic heart ischemia‐reperfusion injury Langendorff system Diseases of the circulatory (Cardiovascular) system RC666-701 Guodong Pan Bipradas Roy Suresh Selvaraj Palaniyandi Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage
description	Background Aldehyde dehydrogenase‐2 (ALDH2), a mitochondrial enzyme, detoxifies reactive aldehydes such as 4‐hydroxy‐2‐nonenal (4HNE). A highly prevalent E487K mutation in ALDH2 (ALDH22) in East Asian people with intrinsic low ALDH2 activity is implicated in diabetic complications. 4HNE‐induced cardiomyocyte dysfunction was studied in diabetic cardiac damage; however, coronary endothelial cell (CEC) injury in myocardial ischemia‐reperfusion injury (IRI) in diabetic mice has not been studied. Therefore, we hypothesize that the lack of ALDH2 activity exacerbates 4HNE‐induced CEC dysfunction which leads to cardiac damage in ALDH22 mutant diabetic mice subjected to myocardial IRI. Methods and Results Three weeks after diabetes mellitus (DM) induction, hearts were subjected to IRI either in vivo via left anterior descending artery occlusion and release or ex vivo IRI by using the Langendorff system. The cardiac performance was assessed by conscious echocardiography in mice or by inserting a balloon catheter in the left ventricle in the ex vivo model. Just 3 weeks of DM led to an increase in cardiac 4HNE protein adducts and, cardiac dysfunction, and a decrease in the number of CECs along with reduced myocardial ALDH2 activity in ALDH22 mutant diabetic mice compared with their wild‐type counterparts. Systemic pretreatment with Alda‐1 (10 mg/kg per day), an activator of both ALDH2 and ALDH22, led to a reduction in myocardial infarct size and dysfunction, and coronary perfusion pressure upon cardiac IRI by increasing CEC population and coronary arteriole opening. Conclusions Low ALDH2 activity exacerbates 4HNE‐mediated CEC injury and thereby cardiac dysfunction in diabetic mouse hearts subjected to IRI, which can be reversed by ALDH2 activation.
format	article
author	Guodong Pan Bipradas Roy Suresh Selvaraj Palaniyandi
author_facet	Guodong Pan Bipradas Roy Suresh Selvaraj Palaniyandi
author_sort	Guodong Pan
title	Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage
title_short	Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage
title_full	Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage
title_fullStr	Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage
title_full_unstemmed	Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage
title_sort	diabetic aldehyde dehydrogenase 2 mutant (aldh2*2) mice are more susceptible to cardiac ischemic‐reperfusion injury due to 4‐hydroxy‐2‐nonenal induced coronary endothelial cell damage
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/6d08815a1b214cd8b9cf068fc03d0cf9
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Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic‐Reperfusion Injury Due to 4‐Hydroxy‐2‐Nonenal Induced Coronary Endothelial Cell Damage

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