ArticleThe Journal of clinical investigation2019
Acetaldehyde dehydrogenase 2 interactions with LDLR and AMPK regulate foam cell formation.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 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
- Genome-wide pQTL mapping in human skin identifies specific genetic regulators and mechanistic links to skin disorders.Nature communications · 2026Article
- E3 ubiquitin ligase TRIM21-mediated K48-linked ubiquitination of ALDH2 rs671 mutant promotes adverse cardiac remodeling.JCI insight · 2026Article
- The Role of Glutathione Peroxidase 4 in Atherosclerosis: Role and Therapeutic Potential.Reviews in cardiovascular medicine · 2026Review
- ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury.Circulation · 2026Article
- Impact of aldehyde dehydrogenase 2 polymorphism on lipid profile alterations in alcohol-abstinent adolescents stratified by steatotic liver disease status.Environmental health and preventive medicine · 2026Article
- ALDH2 in autophagy and cell death: molecular mechanisms and implications for diseases.Military Medical Research · 2025Review
- Exercise Delays Brain Ageing Through Muscle-Brain Crosstalk.Cell proliferation · 2025Review
- Conditioned Medium of BMSCs Alleviates HMolecular neurobiology · 2025Article
- 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
- Combatting sepsis-induced myocardial dysfunction: emerging mechanisms and immunomodulatory breakthroughs.Frontiers in immunology · 2025Review
- The Significance of Aldehyde Dehydrogenase 1 in Cancers.International journal of molecular sciences · 2024Review
- Advances in Factors Affecting ALDH2 Activity and its Mechanisms.Cardiovascular toxicology · 2024Review
- The association between non-HDL cholesterol and high-grade pancreatic neuroendocrine neoplasms.Endocrine · 2024Article
- ALDH2 mediates the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on improving cardiac remodeling.Cardiovascular diabetology · 2024Article
- Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.European heart journal · 2024Article
- Oroxin A fromHeliyon · 2024Article
- Association of liver fibrosis with extrahepatic cancer in steatotic liver disease patients with PNPLA3 I148M GG genotype.Cancer science · 2024Article
- Serum Lipid Level in Evaluating Chinese Pancreatic Neuroendocrine Neoplasms: A Retrospective Study.Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association · 2024Article
- ALDH2 mitigates LPS-induced cardiac dysfunction, inflammation, and apoptosis through the cGAS/STING pathway.Molecular medicine (Cambridge, Mass.) · 2023Article
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12 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Acetaldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme detoxifying acetaldehyde and endogenous lipid aldehydes; previous studies suggest a protective role of ALDH2 against cardiovascular disease (CVD). Around 40% of East Asians carrying the single nucleotide polymorphism (SNP) ALDH2 rs671 have an increased incidence of CVD. However, the role of ALDH2 in CVD beyond alcohol consumption remains poorly defined. Here we report that ALDH2/LDLR double knockout (DKO) mice have decreased atherosclerosis compared with LDLR-KO mice, whereas ALDH2/APOE-DKO mice have increased atherosclerosis, suggesting an unexpected interaction of ALDH2 with LDLR. Further studies demonstrate that in the absence of LDLR, AMPK phosphorylates ALDH2 at threonine 356 and enables its nuclear translocation. Nuclear ALDH2 interacts with HDAC3 and represses transcription of a lysosomal proton pump protein ATP6V0E2, critical for maintaining lysosomal function, autophagy, and degradation of oxidized low-density lipid protein. Interestingly, an interaction of cytosolic LDLR C-terminus with AMPK blocks ALDH2 phosphorylation and subsequent nuclear translocation, whereas ALDH2 rs671 mutant in human macrophages attenuates this interaction, which releases ALDH2 to the nucleus to suppress ATP6V0E2 expression, resulting in increased foam cells due to impaired lysosomal function. Our studies reveal a novel role of ALDH2 and LDLR in atherosclerosis and provide a molecular mechanism by which ALDH2 rs671 SNP increases CVD.
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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.