ArticleScience translational medicine2014
Characterization of the molecular mechanisms underlying increased ischemic damage in the aldehyde dehydrogenase 2 genetic polymorphism using a human induced pluripotent stem cell model system.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Cytokine-associated ROS and Ca2+ dysregulation in severe inflammatory cardiomyopathy.Cardiovascular research · 2026Observational
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- Association of stress hyperglycemia ratio on right ventricular dysfunction and biventricular coupling in patients with acute coronary syndrome assessed by CMR feature tracking: a cross-sectional study.Quantitative imaging in medicine and surgery · 2026Article
- SGLT2 inhibition improves sarcomere contractile dysfunction in human models of dilated cardiomyopathy.Journal of translational medicine · 2026Article
- Targeting intracellular cholesterol imbalance rescues sarcomere-ER contact site signaling and ER remodeling in dilated cardiomyopathy.Signal transduction and targeted therapy · 2026Article
- Sarcomere analysis in human cardiomyocytes by computing radial frequency spectra.Biological chemistry · 2025Article
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- Association between ALDH2 rs671 polymorphism and susceptibility to non-valvular atrial fibrillation in a Chinese population: a large-scale case-control study.Frontiers in physiology · 2025Article
- Advances in Factors Affecting ALDH2 Activity and its Mechanisms.Cardiovascular toxicology · 2024Review
- Investigating Inherited Heart Diseases Using Human Induced Pluripotent Stem Cell-Based Models.Life (Basel, Switzerland) · 2024Review
- Clinical trials in-a-dish for cardiovascular medicine.European heart journal · 2024Review
- Article
- 4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification.European heart journal · 2023Article
- SGLT2 inhibitor ameliorates endothelial dysfunction associated with the commonScience translational medicine · 2023Article
- E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme.Redox biology · 2022Article
- Intersectionality and genetic ancestry: New methods to solve old problems.EBioMedicine · 2022Article
- Computational Investigation of Structural Basis for Enhanced Binding of Isoflavone Analogues with Mitochondrial Aldehyde Dehydrogenase.ACS omega · 2022Article
- HPV E6/E7 promotes aerobic glycolysis in cervical cancer by regulating IGF2BP2 to stabilize mInternational journal of biological sciences · 2022Article
- Deciphering pathogenicity of variants of uncertain significance with CRISPR-edited iPSCs.Trends in genetics : TIG · 2021Review
- ALDH2 deficiency induces atrial fibrillation through dysregulated cardiac sodium channel and mitochondrial bioenergetics: A multi-omics analysis.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Nearly 8% of the human population carries an inactivating point mutation in the gene that encodes the cardioprotective enzyme aldehyde dehydrogenase 2 (ALDH2). This genetic polymorphism (ALDH2*2) is linked to more severe outcomes from ischemic heart damage and an increased risk of coronary artery disease (CAD), but the underlying molecular bases are unknown. We investigated the ALDH2*2 mechanisms in a human model system of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation gave rise to elevated amounts of reactive oxygen species and toxic aldehydes, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. We established that ALDH2 controls cell survival decisions by modulating oxidative stress levels and that this regulatory circuitry was dysfunctional in the loss-of-function ALDH2*2 genotype, causing up-regulation of apoptosis in cardiomyocytes after ischemic insult. These results reveal a new function for the metabolic enzyme ALDH2 in modulation of cell survival decisions. Insight into the molecular mechanisms that mediate ALDH2*2-related increased ischemic damage is important for the development of specific diagnostic methods and improved risk management of CAD and may lead to patient-specific cardiac therapies.
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