| http://purl.uniprot.org/citations/25245387 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25245387 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.org/dc/terms/identifier | "doi:10.1161/hypertensionaha.114.03406"xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/author | "Reynolds J.O."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/author | "Wehrens X.H."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/author | "Reynolds C."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/author | "Lloyd E.E."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/author | "Lawrence W.S."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/author | "Pandit L.M."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/author | "Bryan R.M."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/name | "Hypertension"xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/pages | "1260-1265"xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/title | "TWIK-2 channel deficiency leads to pulmonary hypertension through a rho-kinase-mediated process."xsd:string |
| http://purl.uniprot.org/citations/25245387 | http://purl.uniprot.org/core/volume | "64"xsd:string |
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