ArticleFrontiers in cell and developmental biology2021
Homocysteine Causes Endothelial Dysfunction via Inflammatory Factor-Mediated Activation of Epithelial Sodium Channel (ENaC).
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 30 citations in OpenAlex.
- Pathophysiology of homocysteine: insights into ion channel dysfunction.Pflugers Archiv : European journal of physiology · 2026Review
- Association of serum and vitreous homocysteine and uric acid concentrations with post-vitrectomy prognosis in patients with proliferative diabetic retinopathy.World journal of diabetes · 2026Article
- Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration.Nutrients · 2026Article
- High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression ofNeurobiology of stress · 2025Article
- Clinical efficacy of postauricular injection of Methylprednisolone in the treatment of patients with sudden deafness: A retrospective study.Pakistan journal of medical sciences · 2025Article
- Epithelial sodium channel in dendritic cells participates in high-fat-induced inflammatory responses.Molecular biology reports · 2025Article
- Association of Homocysteine with Cardiac Markers and Inflammatory Indicators in Cardiovascular Diseases: A Comparative Study.ACS omega · 2025Article
- Unraveling the Dyslipidemic Landscape in Moyamoya Disease: OxLDL as a Key Biomarker.CNS neuroscience & therapeutics · 2025Article
- Intracellular Iron Deficiency and Abnormal Metabolism, Not Ferroptosis, Contributes to Homocysteine-Induced Vascular Endothelial Cell Death.Biomedicines · 2024Article
- Advances in the study of the correlation between insulin resistance and infertility.Frontiers in endocrinology · 2024Review
- ALDH2 rs671 and MTHFR rs1801133 polymorphisms are risk factors for arteriosclerosis in multiple arteries.BMC cardiovascular disorders · 2023Article
- Significance of Hyperhomocysteinemia in Immediate As Well As Long-Term Health Risk/s in Women with Polycystic Ovary Syndrome: a Probabilistic Model Using Dynamic Bayesian Network Analysis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Therapeutic effect of folic acid combined with decitabine on diabetic mice.International journal of ophthalmology · 2023Article
- Role of epithelial sodium channel-related inflammation in human diseases.Frontiers in immunology · 2023Review
- Deficiency of B vitamins leads to cholesterol-independent atherogenic transformation of the aorta.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- Aldosterone-stimulated endothelial epithelial sodium channel (EnNaC) plays a role in cold exposure-induced hypertension in rats.Frontiers in pharmacology · 2022Article
- Causal effects of homocysteine levels on the components of sarcopenia: A two-sample mendelian randomization study.Frontiers in genetics · 2022Article
- Association of Homocysteine and Risks of Long-Term Cardiovascular Events and All-Cause Death among Older Patients with Obstructive Sleep Apnea: A Prospective Study.The journal of nutrition, health & aging · 2022Observational
- C677T Gene Polymorphism of MTHFR Is a Risk Factor for Impaired Renal Function in Pregnant Women With Preeclampsia in the Chinese Han Population.Frontiers in cardiovascular medicine · 2022Article
- Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person.The EPMA journal · 2021Review
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15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHyperhomocysteinemia (HHcy) causes cardiovascular diseases via regulating inflammatory responses. We investigated whether and how the epithelial sodium channel (ENaC), a recently identified ion channel in endothelial cells, plays a role in HHcy-induced endothelial dysfunction.
methodsCell-attached patch-clamp recording in acute split-open aortic endothelial cells, western blot, confocal imaging, and wire myograph combined with pharmacological approaches were used to determine whether HHcy-mediated inflammatory signaling leads to endothelial dysfunction via stimulating ENaC.
resultsThe data showed that 4 weeks after L-methionine diet the levels of plasma Hcy were significantly increased and the ENaC was dramatically activated in mouse aortic endothelial cells. Administration of benzamil, a specific ENaC blocker, ameliorated L-methionine diet-induced impairment of endothelium-dependent relaxation (EDR) and reversed Hcy-induced increase in ENaC activity. Pharmacological inhibition of NADPH oxidase, reactive oxygen species (ROS), cyclooxygenase-2 (COX-2)/thromboxane B2 (TXB2), or serum/glucocorticoid regulated kinase 1 (SGK1) effectively attenuated both the Hcy-induced activation of endothelial ENaC and impairment of EDR. Our
conclusionWe show that Hcy activates endothelial ENaC and subsequently impairs EDR of mouse aorta, via ROS/COX-2-dependent activation of SGK-1/Nedd4-2 signaling. Our study provides a rational that blockade of the endothelial ENaC could be potential method to prevent and/or to treat Hcy-induced cardiovascular disease.
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