ArticleHypertension (Dallas, Tex. : 1979)2014
TWIK-2 channel deficiency leads to pulmonary hypertension through a rho-kinase-mediated process.
Article in Hypertension (Dallas, Tex. : 1979), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Structural evidence that a lipid plug controls KNature communications · 2026Article
- KPharmaceuticals (Basel, Switzerland) · 2026Review
- Cardiac Manifestations ofHealth science reports · 2026Review
- Insights into the structure and modulation of human TWIK-2.Nature communications · 2026Article
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Inhibition of BMPER Mitigates Pulmonary Hypertension by Modulating LRP1-YAP Interaction in Smooth Muscle Cells.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Article
- Structure of the human TWIK-2 potassium channel and its inhibition by pimozide.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The TWIK2-mtDNA-NLRP3 inflammasome signaling in hepatic macrophages facilitates exercise-induced attenuation of hepatic inflammation and insulin resistance in db/db mice.Journal of physiology and biochemistry · 2025Article
- Up-regulated expression of two-pore domain KFrontiers in cardiovascular medicine · 2024Article
- Endosomal trafficking of two-pore KeLife · 2023Article
- Perinatal Lead Exposure Promotes Sex-Specific Epigenetic Programming of Disease-Relevant Pathways in Mouse Heart.Toxics · 2023Article
- Genome-wide search identified DNA methylation sites that regulate the metabolome.Frontiers in genetics · 2023Article
- Review
- Channelopathy Genes in Pulmonary Arterial Hypertension.Biomolecules · 2022Review
- Two-Pore-Domain Potassium (KCells · 2021Review
- Transcriptomic profile of cationic channels in human pulmonary arterial hypertension.Scientific reports · 2021Article
- Potassium Channel Protein KCNK6 Promotes Breast Cancer Cell Proliferation, Invasion, and Migration.Frontiers in cell and developmental biology · 2021Article
- Vasoconstrictor Mechanisms in Chronic Hypoxia-Induced Pulmonary Hypertension: Role of Oxidant Signaling.Antioxidants (Basel, Switzerland) · 2020Review
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7 authors.
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Abstract
TWIK-2 (KCNK6) is a member of the 2-pore domain (K2P) family of potassium channels, which are highly expressed in the vascular system. We tested the hypothesis that TWIK-2 deficiency leads to pulmonary hypertension. TWIK-2 knockout mice and their wildtype littermates at 8 weeks of age had similar mean right ventricular systolic pressures (24±3 and 21±3 mm Hg, respectively.) Significantly, by 20 weeks of age, the mean right ventricular systolic pressures in TWIK-2 knockout mice increased to 35±3 mm Hg (P≤0.036), whereas mean right ventricular systolic pressures in wildtype littermates remained at 22±3 mm Hg. Elevated mean right ventricular systolic pressures in the TWIK-2 knockout mice was accompanied by pulmonary vascular remodeling as determined by a 25% increase in the cross-sectional area of the vessels occupied by the vessel wall. Additionally, secondary branches of the pulmonary artery from 20-week-old TWIK-2 knockout mice showed an enhanced contractile response to U46619 (10(-6) moles/L), a thromboxane A2 mimetic, which was completely abolished with the Rho-kinase inhibitor, Y27632 (10(-6) and 10(-5) moles/L). Treatment of TWIK-2 knockout mice with the Rho-kinase inhibitor, fasudil, in the drinking water for 12 weeks, abolished the development of pulmonary hypertension and attenuated the vessel remodeling. We concluded that mice deficient in the TWIK-2 channel develop pulmonary hypertension between 8 and 20 weeks of age through a mechanism involving Rho-kinase. Our results suggest that downregulation of TWIK-2 in the pulmonary vasculature may be an underlying mechanism in the development of pulmonary hypertension.
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