ArticleFree radical biology & medicine2014
Mitochondrial aldehyde dehydrogenase 2 accentuates aging-induced cardiac remodeling and contractile dysfunction: role of AMPK, Sirt1, and mitochondrial function.
Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 133 citations in OpenAlex.
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- Long-term multi-organ system abnormalities in mice exposed to antenatal and postnatal corticosteroids.Pediatric research · 2026Article
- Molecular Mediators of the Cardiac Benefits of Exercise.Circulation research · 2025Review
- Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment.Cardiovascular diabetology · 2025Review
- Aldehyde Dehydrogenase 2 Gene Mutation May Reduce the Risk of Rupture of Intracranial Aneurysm in Chinese Han Population.Journal of stroke · 2025Article
- N6-methyladenosine RNA landscape in the aged mouse hearts.Frontiers in cardiovascular medicine · 2025Article
- The Cognitive Restoration Effects of Resveratrol: Insight Molecular through Behavioral Studies in Various Cognitive Impairment Models.ACS pharmacology & translational science · 2024Review
- UCP2, a Member of the Mitochondrial Uncoupling Proteins: An Overview from Physiological to Pathological Roles.Biomedicines · 2024Review
- Cardiovascular aging: spotlight on mitochondria.American journal of physiology. Heart and circulatory physiology · 2024Review
- Colchicine ameliorates myocardial injury induced by coronary microembolization through suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway.BMC cardiovascular disorders · 2024Article
- SGLT2 inhibitor empagliflozin alleviates cardiac remodeling and contractile anomalies in a FUNDC1-dependent manner in experimental Parkinson's disease.Acta pharmacologica Sinica · 2024Article
- Selective inhibition of the NLRP3 inflammasome protects against acute ethanol-induced cardiotoxicity in an FBXL2-dependent manner.Acta biochimica et biophysica Sinica · 2023Article
- The role of aldehyde dehydrogenase 2 in cardiovascular disease.Nature reviews. Cardiology · 2023Review
- Activation of the sirtuin silent information regulator 1 pathway inhibits pathological myocardial remodeling.Frontiers in pharmacology · 2023Review
- The dynamic interplay between cardiac mitochondrial health and myocardial structural remodeling in metabolic heart disease, aging, and heart failure.The journal of cardiovascular aging · 2023Article
- CoQNutrients · 2022Review
- lncRNA NBR2 attenuates angiotensin II-induced myocardial hypertrophy through repressing ER stress via activating LKB1/AMPK/Sirt1 pathway.Bioengineered · 2022Article
- Increase of Oxidative Stress by Deficiency of The ALDH2/UCP2/Nrf2 Axis Exacerbates Cardiac Dysfunction in Chronic Kidney Disease.Reviews in cardiovascular medicine · 2022Article
- Single-Cell Analysis Reveals Transcriptomic Reprogramming in Aging Cardiovascular Endothelial Cells.Frontiers in cardiovascular medicine · 2022Article
- Uncoupling Protein 2 as a Pathogenic Determinant and Therapeutic Target in Cardiovascular and Metabolic Diseases.Current neuropharmacology · 2022Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac aging is associated with compromised myocardial function and morphology although the underlying mechanism remains elusive. Aldehyde dehydrogenase 2 (ALDH2), an essential mitochondrial enzyme governing cardiac function, displays polymorphism in humans. This study was designed to examine the role of ALDH2 in aging-induced myocardial anomalies. Myocardial mechanical and intracellular Ca(2+) properties were examined in young (4-5 months) and old (26-28 months) wild-type and ALDH2 transgenic mice. Cardiac histology, mitochondrial integrity, O2(-) generation, apoptosis, and signaling cascades, including AMPK activation and Sirt1 level were evaluated. Myocardial function and intracellular Ca(2+) handling were compromised with advanced aging; the effects were accentuated by ALDH2. Hematoxylin and eosin and Masson trichrome staining revealed cardiac hypertrophy and interstitial fibrosis associated with greater left-ventricular mass and wall thickness in aged mice. ALDH2 accentuated aging-induced cardiac hypertrophy but not fibrosis. Aging promoted O2(-) release, apoptosis, and mitochondrial injury (mitochondrial membrane potential, levels of UCP-2 and PGC-1α), and the effects were also exacerbated by ALDH2. Aging dampened AMPK phosphorylation and Sirt1, the effects of which were exaggerated by ALDH2. Treatment with the ALDH2 activator Alda-1 accentuated aging-induced O2(-) generation and mechanical dysfunction in cardiomyocytes, the effects of which were mitigated by cotreatment with activators of AMPK and Sirt1, AICAR, resveratrol, and SRT1720. Examination of human longevity revealed a positive correlation between life span and ALDH2 gene mutation. Taken together, our data revealed that ALDH2 enzyme may accentuate myocardial remodeling and contractile dysfunction in aging, possibly through AMPK/Sirt1-mediated mitochondrial injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.