ArticleRedox biology2017
Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension.
Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Association Between ALDH-2 rs671 and Essential Hypertension Risk or Blood Pressure Levels: A Systematic Review and Meta-Analysis.Frontiers in genetics · 2020Pooled it
- Monocrotaline toxicity in rats: decreased lung retinol and elevated alpha-tocopherol levels in lung and liver.Journal of nutritional science · 2026Article
- The interplay of ferroptosis and oxidative stress in pulmonary fibrosis: from mechanisms to treatment.Frontiers in cell and developmental biology · 2026Review
- Plasma 4-hydroxynonenal estimates severity and prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease.Scientific reports · 2025Article
- Shared genetic architecture between stroke and blood lipids: a large-scale genome-wide cross-trait analysis.Human genomics · 2025Article
- Role of Ferroptosis in Alveolar Epithelial Cells in Acute Respiratory Distress Syndrome.Journal of inflammation research · 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
- Article
- [Activation of ALDH2 alleviates hypoxic pulmonary hypertension in mice by upregulating the SIRT1/PGC-1α signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Study on the mechanism of echinacoside in preventing and treating hypoxic pulmonary hypertension based on proteomic analyses.Pharmacology research & perspectives · 2024Article
- The role of aldehyde dehydrogenase 2 in cardiovascular disease.Nature reviews. Cardiology · 2023Review
- Article
- Association of Different Combinations ofInternational journal of general medicine · 2023Article
- Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction.Biomolecules · 2022Review
- E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme.Redox biology · 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
- Aldehyde Dehydrogenase 2 (ALDH2) Elicits Protection against Pulmonary Hypertension via Inhibition of ERK1/2-Mediated Autophagy.Oxidative medicine and cellular longevity · 2022Article
- The Potential Role of Mitochondrial Acetaldehyde Dehydrogenase 2 in Urological Cancers From the Perspective of Ferroptosis and Cellular Senescence.Frontiers in cell and developmental biology · 2022Review
- Environmental toxicant-induced maladaptive mitochondrial changes: A potential unifying mechanism in fatty liver disease?Acta pharmaceutica Sinica. B · 2021Review
- Involvement of 4-hydroxy-2-nonenal in the pathogenesis of pulmonary fibrosis.Molecular and cellular biochemistry · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cardioprotective benefits of aldehyde dehydrogenase 2 (ALDH2) are well established, although the regulatory role of ALDH2 in vascular remodeling in pulmonary arterial hypertension (PAH) is largely unknown. ALDH2 potently regulates the metabolism of aldehydes such as 4-hydroxynonenal (4-HNE), the endogenous product of lipid peroxidation. Thus, we hypothesized that ALDH2 ameliorates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting 4-HNE accumulation and regulating downstream signaling pathways, thereby ameliorating pulmonary vascular remodeling. We found that low concentrations of 4-HNE (0.1 and 1μM) stimulated cell proliferation by enhancing cyclin D1 and c-Myc expression in primary HPASMCs. Low 4-HNE concentrations also enhanced cell migration by activating the nuclear factor kappa B (NF-κB) signaling pathway, thereby regulating matrix metalloprotein (MMP)-9 and MMP2 expression in vitro. In vivo, Alda-1, an ALDH2 agonist, significantly stimulated ALDH2 activity, reducing elevated 4-HNE and malondialdehyde levels and right ventricular systolic pressure in a monocrotaline-induced PAH animal model to the level of control animals. Our findings indicate that 4-HNE plays an important role in the abnormal proliferation and migration of HPASMCs, and that ALDH2 activation can attenuate 4-HNE-induced PASMC proliferation and migration, possibly by regulating NF-κB activation, in turn ameliorating vascular remodeling in PAH. This mechanism might reflect a new molecular target for treating PAH.
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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.