ArticleJournal of the American Heart Association2021
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.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- The ALDH2 gene rs671 polymorphism is associated with cardiometabolic risk factors in East Asian population: an updated meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- ALDH2 Mediated Ferroptosis Regulation in Ischemia-Reperfusion Injury.Journal of cellular and molecular medicine · 2026Review
- Article
- Role of ALDH2 in myocardial ischemia-reperfusion injury: using ALDH2 as a potential therapeutic target.Frontiers in pharmacology · 2026Review
- Targeted Overexpression of Mitochondrial ALDH2 in Coronary Endothelial Cells Mitigates HFpEF in a Diabetic Mouse Model.Biomolecules · 2025Article
- Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).Molecular medicine reports · 2025Review
- Mitochondrial DNA variants in the pathogenesis and metabolic alterations of diabetes mellitus.Molecular genetics and metabolism reports · 2025Review
- ZBiotics ameliorates T2DM-induced histopathological damage in liver, kidney and adipose tissues by modulating the NOD-like receptor signaling in Wistar rats.Diabetology & metabolic syndrome · 2025Article
- Geographical distribution of ALDH2 rs671 polymorphism in Chinese angina pectoris patients.Frontiers in genetics · 2025Article
- Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.European heart journal · 2024Article
- Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.Journal of translational medicine · 2023Review
- Effects of intracardiac delivery of aldehyde dehydrogenase 2 gene in myocardial salvage.Gene therapy · 2023Article
- SGLT2 inhibitor ameliorates endothelial dysfunction associated with the commonScience translational medicine · 2023Article
- Aldehyde Dehydrogenase 2 Activator Augments the Beneficial Effects of Empagliflozin in Mice with Diabetes-Associated HFpEF.International journal of molecular sciences · 2022Article
- E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme.Redox biology · 2022Article
- Article
- Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting ApoptosisFrontiers in pharmacology · 2022Article
- Pharmacological Activation Of Aldehyde Dehydrogenase 2 Protects Against Heatstroke-Induced Acute Lung Injury by Modulating Oxidative Stress and Endothelial Dysfunction.Frontiers in immunology · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
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 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 ALDH2*2 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 ALDH2*2 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.
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