ArticleAmerican journal of physiology. Heart and circulatory physiology2016
20-HETE-induced mitochondrial superoxide production and inflammatory phenotype in vascular smooth muscle is prevented by glucose-6-phosphate dehydrogenase inhibition.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Extreme Diversity of the Human Vascular Mesenchymal Cell Landscape.Journal of the American Heart Association · 2020Pooled it
- Reduced circulating 20-hydroxyeicosatetraenoic acid and ACE2 in acute coronary syndrome with exploratory cell-based observations.Scientific reports · 2026Article
- Blood multiomics reveal a dysregulated lipid mediator-mitochondrial network associated with the outcome of advanced cirrhosis.Nature communications · 2026Article
- Reprogrammed glucose metabolism in vascular smooth muscle cells and its implications for vascular diseases.Pharmacological research · 2025Review
- Methylseq, single-nuclei RNAseq, and discovery proteomics identify pathways associated with nephron-deficit CKD in the HSRA rat model.American journal of physiology. Renal physiology · 2025Article
- Omega-6 polyunsaturated fatty acids and their metabolites: a potential targeted therapy for pulmonary hypertension.Respiratory research · 2025Review
- Global and endothelial G-protein coupled receptor 75 (GPR75) knockout relaxes pulmonary artery and mitigates hypoxia-induced pulmonary hypertension.Vascular pharmacology · 2023Article
- Gpr75-deficient mice are protected from high-fat diet-induced obesity.Obesity (Silver Spring, Md.) · 2023Article
- Relationship between Glucose-6-Phosphate Dehydrogenase Deficiency, X-Chromosome Inactivation and Inflammatory Markers.Antioxidants (Basel, Switzerland) · 2023Article
- 20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Hyperoxia evokes pericyte-mediated capillary constriction.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Signal Transduction during Metabolic and Inflammatory Reprogramming in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2022Review
- Mitochondrial Metabolism, Redox, and Calcium Homeostasis in Pulmonary Arterial Hypertension.Biomedicines · 2022Review
- The CYP/20-HETE/GPR75 axis in hypertension.Advances in pharmacology (San Diego, Calif.) · 2022Review
- 20-HETE synthesis inhibition attenuates traumatic brain injury-induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC-1α pathway: A translational study.Cell proliferation · 2021Article
- 20-HETE interferes with insulin signaling and contributes to obesity-driven insulin resistance.Prostaglandins & other lipid mediators · 2021Article
- Glucose-6-phosphate dehydrogenase increases CaAmerican journal of physiology. Heart and circulatory physiology · 2020Article
- 20-HETE in the regulation of vascular and cardiac function.Pharmacology & therapeutics · 2018Review
- High-fat diet-induced obesity and insulin resistance in CYP4a14American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Hallmarks of Pulmonary Hypertension: Mesenchymal and Inflammatory Cell Metabolic Reprogramming.Antioxidants & redox signaling · 2018Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
20-Hydroxyeicosatetraeonic acid (20-HETE) produced by cytochrome P-450 monooxygenases in NADPH-dependent manner is proinflammatory, and it contributes to the pathogenesis of systemic and pulmonary hypertension. In this study, we tested the hypothesis that inhibition of glucose-6-phosphate dehydrogenase (G6PD), a major source of NADPH in the cell, prevents 20-HETE synthesis and 20-HETE-induced proinflammatory signaling that promotes secretory phenotype of vascular smooth muscle cells. Lipidomic analysis indicated that G6PD inhibition and knockdown decreased 20-HETE levels in pulmonary arteries as well as 20-HETE-induced 1) mitochondrial superoxide production, 2) activation of mitogen-activated protein kinase 1 and 3, 3) phosphorylation of ETS domain-containing protein Elk-1 that activate transcription of tumor necrosis factor-α gene (Tnfa), and 4) expression of tumor necrosis factor-α (TNF-α). Moreover, inhibition of G6PD increased protein kinase G1α activity, which, at least partially, mitigated superoxide production and Elk-1 and TNF-α expression. Additionally, we report here for the first time that 20-HETE repressed miR-143, which suppresses Elk-1 expression, and miR-133a, which is known to suppress synthetic/secretory phenotype of vascular smooth muscle cells. In summary, our findings indicate that 20-HETE elicited mitochondrial superoxide production and promoted secretory phenotype of vascular smooth muscle cells by activating MAPK1-Elk-1, all of which are blocked by inhibition of G6PD.
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