ArticleThe Journal of biological chemistry2016
Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is Necessary and Sufficient for Vascular Bioactivation of Nitroglycerin.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Influence of the aldehyde dehydrogenase 2 polymorphism on the vasodilatory effect of nitroglycerin in infants with congenital heart disease and pulmonary arterial hypertension.European journal of clinical pharmacology · 2019Trial
- Shared genetic architecture between stroke and blood lipids: a large-scale genome-wide cross-trait analysis.Human genomics · 2025Article
- Geographical distribution of ALDH2 rs671 polymorphism in Chinese angina pectoris patients.Frontiers in genetics · 2025Article
- Human Aldehyde Dehydrogenases: A Superfamily of Similar Yet Different Proteins Highly Related to Cancer.Cancers · 2023Review
- Nitroglycerin: a comprehensive review in cancer therapy.Cell death & disease · 2023Review
- Association of Different Combinations ofInternational journal of general medicine · 2023Article
- Article
- Alcohol flushing syndrome is significantly associated with intracranial aneurysm rupture in the Chinese Han population.Frontiers in neurology · 2023Article
- Probing Subcellular Iron Availability with Genetically Encoded Nitric Oxide Biosensors.Biosensors · 2022Article
- A physiologically relevant role for NO stored in vascular smooth muscle cells: A novel theory of vascular NO signaling.Redox biology · 2022Review
- Nitric oxide biosensor uncovers diminished ferrous iron-dependency of cultured cells adapted to physiological oxygen levels.Redox biology · 2022Article
- Multitarget Antioxidant NO-Donor Organic Nitrates: A Novel Approach to Overcome Nitrates Tolerance, an Ex Vivo Study.Antioxidants (Basel, Switzerland) · 2022Article
- Novel and prevalent non-East Asian ALDH2 variants; Implications for global susceptibility to aldehydes' toxicity.EBioMedicine · 2020Article
- Endothelial Aldehyde Dehydrogenase 2 as a Target to Maintain Vascular Wellness and Function in Ageing.Biomedicines · 2020Review
- Discordance between eNOS phosphorylation and activation revealed by multispectral imaging and chemogenetic methods.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- L-NAME releases nitric oxide and potentiates subsequent nitroglycerin-mediated vasodilation.Redox biology · 2019Article
- Genetic biosensors for imaging nitric oxide in single cells.Free radical biology & medicine · 2018Review
- Sustained Formation of Nitroglycerin-Derived Nitric Oxide by Aldehyde Dehydrogenase-2 in Vascular Smooth Muscle without Added Reductants: Implications for the Development of Nitrate Tolerance.Molecular pharmacology · 2018Article
- Nitroglycerin application and coronary arteriogenesis.PloS one · 2018Article
- Real-time visualization of distinct nitric oxide generation of nitric oxide synthase isoforms in single cells.Nitric oxide : biology and chemistry · 2017Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate cyclase (sGC) and cGMP-mediated vasodilation. We have previously shown that a minor reaction of ALDH2-catalyzed GTN bioconversion, accounting for about 5% of the main clearance-based turnover yielding inorganic nitrite, results in direct NO formation and concluded that this minor pathway could provide the link between vascular GTN metabolism and activation of sGC. However, lack of detectable NO at therapeutically relevant GTN concentrations (≤1 μm) in vascular tissue called into question the biological significance of NO formation by purified ALDH2. We addressed this issue and used a novel, highly sensitive genetically encoded fluorescent NO probe (geNOp) to visualize intracellular NO formation at low GTN concentrations (≤1 μm) in cultured vascular smooth muscle cells (VSMC) expressing an ALDH2 mutant that reduces GTN to NO but lacks clearance-based GTN denitration activity. NO formation was compared with GTN-induced activation of sGC. The addition of 1 μm GTN to VSMC expressing either wild-type or C301S/C303S ALDH2 resulted in pronounced intracellular NO elevation, with maximal concentrations of 7 and 17 nm, respectively. Formation of GTN-derived NO correlated well with activation of purified sGC in VSMC lysates and cGMP accumulation in intact porcine aortic endothelial cells infected with wild-type or mutant ALDH2. Formation of NO and cGMP accumulation were inhibited by ALDH inhibitors chloral hydrate and daidzin. The present study demonstrates that ALDH2-catalyzed NO formation is necessary and sufficient for GTN bioactivation in VSMC.
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