{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:00:46Z","timestamp":1787162446810,"version":"build-2736575974"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"14","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,4,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>G protein\u2013coupled receptors are important regulators of contractility and differentiation in vascular smooth muscle cells (SMCs), but the specific function of SMC-expressed orphan G protein\u2013coupled receptor class C group 5 member B (GPRC5B) is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We studied the role of GPRC5B in the regulation of contractility and dedifferentiation in human and murine SMCs in vitro and in iSM-\n                      <jats:italic>Gprc5b<\/jats:italic>\n                      -KO (tamoxifen-inducible, SMC-specific knockout) mice under conditions of arterial hypertension and atherosclerosis in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Mesenteric arteries from SMC-specific\n                      <jats:italic>Gprc5b<\/jats:italic>\n                      -KOs showed ex vivo significantly enhanced prostacyclin receptor (IP)\u2013dependent relaxation, whereas responses to other relaxant or contractile factors were normal. In vitro, knockdown of GPRC5B in human aortic SMCs resulted in increased IP-dependent cAMP production and consecutive facilitation of SMC relaxation. In line with this facilitation of IP-mediated relaxation, iSM-\n                      <jats:italic>Gprc5b<\/jats:italic>\n                      -KO mice were protected from arterial hypertension, and this protective effect was abrogated by IP antagonists. Mechanistically, we show that knockdown of GPRC5B increased the membrane localization of IP both in vitro and in vivo and that GPRC5B, but not other G protein\u2013coupled receptors, physically interacts with IP. Last, we show that enhanced IP signaling in GPRC5B-deficient SMCs not only facilitates relaxation but also prevents dedifferentiation during atherosclerosis development, resulting in reduced plaque load and increased differentiation of SMCs in the fibrous cap.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Taken together, our data show that GPRC5B regulates vascular SMC tone and differentiation by negatively regulating IP signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.119.043703","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T05:02:27Z","timestamp":1579150947000},"page":"1168-1183","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Orphan G Protein\u2013Coupled Receptor GPRC5B Controls Smooth Muscle Contractility and Differentiation by Inhibiting Prostacyclin Receptor Signaling"],"prefix":"10.1161","volume":"141","author":[{"given":"Jorge","family":"Carvalho","sequence":"first","affiliation":[{"name":"Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Chennupati","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"ECCPS Deep Sequencing Platform (S.G.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harmandeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Tonack","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kurz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Philipps-University Marburg, Germany (M.K., N.M., M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"M\u00f6\u00dflein","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Philipps-University Marburg, Germany (M.K., N.M., M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"B\u00fcnemann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacy, Philipps-University Marburg, Germany (M.K., N.M., M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (J.C., R.C., R.L., H.K., W.Z., S.T., S.O., N.W.), Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany."},{"name":"Medical Faculty, J.W. 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