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• W4319294663 abstract "Mutations in BMPR2 (bone morphogenetic protein receptor 2) are associated with familial and sporadic pulmonary arterial hypertension (PAH). The functional and molecular link between loss of BMPR2 in pulmonary artery smooth muscle cells (PASMC) and PAH pathogenesis warrants further investigation, as most investigations focus on BMPR2 in pulmonary artery endothelial cells. Our goal was to determine whether and how decreased BMPR2 is related to the abnormal phenotype of PASMC in PAH.SMC-specific Bmpr2-/- mice (BKOSMC) were created and compared to controls in room air, after 3 weeks of hypoxia as a second hit, and following 4 weeks of normoxic recovery. Echocardiography, right ventricular systolic pressure, and right ventricular hypertrophy were assessed as indices of pulmonary hypertension. Proliferation, contractility, gene and protein expression of PASMC from BKOSMC mice, human PASMC with BMPR2 reduced by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation were compared to controls, to investigate the phenotype and underlying mechanism.BKOSMC mice showed reduced hypoxia-induced vasoconstriction and persistent pulmonary hypertension following recovery from hypoxia, associated with sustained muscularization of distal pulmonary arteries. PASMC from mutant compared to control mice displayed reduced contractility at baseline and in response to angiotensin II, increased proliferation and apoptosis resistance. Human PASMC with reduced BMPR2 by small interference RNA, and PASMC from PAH patients with a BMPR2 mutation showed a similar phenotype related to upregulation of pERK1/2 (phosphorylated extracellular signal related kinase 1/2)-pP38-pSMAD2/3 mediating elevation in ARRB2 (β-arrestin2), pAKT (phosphorylated protein kinase B) inactivation of GSK3-beta, CTNNB1 (β-catenin) nuclear translocation and reduction in RHOA (Ras homolog family member A) and RAC1 (Ras-related C3 botulinum toxin substrate 1). Decreasing ARRB2 in PASMC with reduced BMPR2 restored normal signaling, reversed impaired contractility and attenuated heightened proliferation and in mice with inducible loss of BMPR2 in SMC, decreasing ARRB2 prevented persistent pulmonary hypertension.Agents that neutralize the elevated ARRB2 resulting from loss of BMPR2 in PASMC could prevent or reverse the aberrant hypocontractile and hyperproliferative phenotype of these cells in PAH." @default.
• W4319294663 created "2023-02-07" @default.
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• W4319294663 date "2023-03-03" @default.
• W4319294663 modified "2023-10-16" @default.
• W4319294663 title "Dysregulated Smooth Muscle Cell BMPR2–ARRB2 Axis Causes Pulmonary Hypertension" @default.
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• W4319294663 cites W1973508839 @default.
• W4319294663 cites W1976704214 @default.
• W4319294663 cites W1978945918 @default.
• W4319294663 cites W1999275474 @default.
• W4319294663 cites W2002925464 @default.
• W4319294663 cites W2014217144 @default.
• W4319294663 cites W2014973010 @default.
• W4319294663 cites W2020646157 @default.
• W4319294663 cites W2021511409 @default.
• W4319294663 cites W2028304435 @default.
• W4319294663 cites W2030470655 @default.
• W4319294663 cites W2039879879 @default.
• W4319294663 cites W2045789824 @default.
• W4319294663 cites W2046393134 @default.
• W4319294663 cites W2062009083 @default.
• W4319294663 cites W2075536398 @default.
• W4319294663 cites W2076168873 @default.
• W4319294663 cites W2083998789 @default.
• W4319294663 cites W2090205498 @default.
• W4319294663 cites W2101098809 @default.
• W4319294663 cites W2105921136 @default.
• W4319294663 cites W2105948527 @default.
• W4319294663 cites W2108803085 @default.
• W4319294663 cites W2115957792 @default.
• W4319294663 cites W2117041380 @default.
• W4319294663 cites W2124907310 @default.
• W4319294663 cites W2128455103 @default.
• W4319294663 cites W2130632774 @default.
• W4319294663 cites W2137527329 @default.
• W4319294663 cites W2140109458 @default.
• W4319294663 cites W2140154776 @default.
• W4319294663 cites W2143227312 @default.
• W4319294663 cites W2144790255 @default.
• W4319294663 cites W2146888695 @default.
• W4319294663 cites W2147791685 @default.
• W4319294663 cites W2148626940 @default.
• W4319294663 cites W2152501741 @default.
• W4319294663 cites W2152673117 @default.
• W4319294663 cites W2153189553 @default.
• W4319294663 cites W2153638986 @default.
• W4319294663 cites W2155728050 @default.
• W4319294663 cites W2157122261 @default.
• W4319294663 cites W2158636205 @default.
• W4319294663 cites W2163737997 @default.
• W4319294663 cites W2200906169 @default.
• W4319294663 cites W2341828371 @default.
• W4319294663 cites W2573997978 @default.
• W4319294663 cites W2597245371 @default.
• W4319294663 cites W2767249722 @default.
• W4319294663 cites W2885686642 @default.
• W4319294663 cites W2900986057 @default.
• W4319294663 cites W2903848341 @default.
• W4319294663 cites W2913014410 @default.
• W4319294663 cites W2951410937 @default.
• W4319294663 cites W3111447194 @default.
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• W4319294663 doi "https://doi.org/10.1161/circresaha.121.320541" @default.
• W4319294663 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36744494" @default.
• W4319294663 hasPublicationYear "2023" @default.
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