ArticleRedox biology2019
Knockout of dihydrofolate reductase in mice induces hypertension and abdominal aortic aneurysm via mitochondrial dysfunction.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Targeting REV-ERBα/BNIP3 axis attenuates pulmonary arterial hypertension by repressing mitophagy in mice.Nature communications · 2026Article
- eNOS Uncoupling-ER Stress-Mitochondrial Dysfunction Axis in the Development of Pulmonary Hypertension.JACC. Basic to translational science · 2026Article
- Attenuation of advanced atherosclerosis and aortic aneurysm in hph-1/apoE DKO mice by folic acid and DHFR overexpression.Frontiers in physiology · 2026Article
- Comprehensive analysis the role of cuproptosis related genes in abdominal aortic aneurysm.Annals of medicine and surgery (2012) · 2025Article
- The impact of folic acid/VB12 deficiency on essential hypertension in children and adolescents: from a nested case-control and a cohort study.Journal of human hypertension · 2024Article
- Macrophage polarization and metabolic reprogramming in abdominal aortic aneurysm.Immunity, inflammation and disease · 2024Review
- Reversal of Pulmonary Hypertension in a Human-Like Model: Therapeutic Targeting of Endothelial DHFR.Circulation research · 2024Article
- Natural compounds targeting mitochondrial dysfunction: emerging therapeutics for target organ damage in hypertension.Frontiers in pharmacology · 2023Review
- Increased plasma renin by vasodilators promotes the progression of abdominal aortic aneurysm.Frontiers in pharmacology · 2023Article
- Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication.Redox biology · 2022Article
- The role of phosphoinositide 3-kinases in immune-inflammatory responses: potential therapeutic targets for abdominal aortic aneurysm.Cell cycle (Georgetown, Tex.) · 2022Review
- Diagnostic and predictive values of circulating tetrahydrobiopterin levels as a novel biomarker in patients with thoracic and abdominal aortic aneurysms.Redox biology · 2022Article
- Endothelial Dysfunction in the Pathogenesis of Abdominal Aortic Aneurysm.Biomolecules · 2022Review
- Targeting MicroRNA-192-5p, a Downstream Effector of NOXs (NADPH Oxidases), Reverses Endothelial DHFR (Dihydrofolate Reductase) Deficiency to Attenuate Abdominal Aortic Aneurysm Formation.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Targeting mitochondrial fission as a potential therapeutic for abdominal aortic aneurysm.Cardiovascular research · 2021Article
- Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases.Frontiers in immunology · 2021Review
- Potential Roles of Endoplasmic Reticulum Stress and Cellular Proteins Implicated in Diabesity.Oxidative medicine and cellular longevity · 2021Review
- Article
- Age-related mitochondrial dysfunction as a key factor in COVID-19 disease.Experimental gerontology · 2020Review
- NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets.Nature reviews. Cardiology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hypertension and abdominal aortic aneurysm (AAA) are severe cardiovascular diseases with incompletely defined molecular mechanisms. In the current study we generated dihydrofolate reductase (DHFR) knockout mice for the first time to examine its potential contribution to the development of hypertension and AAA, as well as the underlying molecular mechanisms. Whereas the homozygote knockout mice were embryonically lethal, the heterozygote knockout mice had global reduction in DHFR protein expression and activity. Angiotensin II infusion into these animals resulted in substantially exaggerated elevation in blood pressure and development of AAA, which was accompanied by excessive eNOS uncoupling activity (featured by significantly impaired tetrahydrobiopterin and nitric oxide bioavailability), vascular remodeling (MMP2 activation, medial elastin breakdown and adventitial fibrosis) and inflammation (macrophage infiltration). Importantly, scavenging of mitochondrial reactive oxygen species with Mito-Tempo in vivo completely abrogated development of hypertension and AAA in DHFR knockout mice, indicating a novel role of mitochondria in mediating hypertension and AAA downstream of DHFR deficiency-dependent eNOS uncoupling. These data for the first time demonstrate that targeting DHFR-deficiency driven mitochondrial dysfunction may represent an innovative therapeutic option for the treatment of AAA and hypertension.
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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.