{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T07:11:00Z","timestamp":1773645060656,"version":"3.50.1"},"reference-count":72,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Smooth muscle cells (SMCs) regulate blood flow distribution via vasoconstriction mediated by \u03b1-ARs (\u03b1-adrenergic receptors). Plasma membrane cholesterol accumulation affects \u03b1\n              <jats:sub>1<\/jats:sub>\n              -AR signaling and promotes loss of SMC contractile markers in vitro. ABCA1 and ABCG1 (ATP-binding cassette transporter A1 and G1) mediate cholesterol efflux to HDL (high-density lipoprotein). ABCA1\/ABCG1 show high expression in medial and low expression in intimal SMCs of atherosclerotic plaques. The role of ABCA1 and ABCG1 in SMC-mediated vasoconstriction and atherogenesis remains poorly understood.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              We generated mice with SMC-specific\n              <jats:italic>Abca1\/Abcg1<\/jats:italic>\n              deficiency on the low-density lipoprotein receptor\u2013deficient (\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212<\/jats:italic>\n              <\/jats:sup>\n              <jats:sup>\n                <jats:italic>\/<\/jats:italic>\n              <\/jats:sup>\n              <jats:sup>\n                <jats:italic>\u2212<\/jats:italic>\n              <\/jats:sup>\n              ) background by crossbreeding\n              <jats:italic>Abca1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>fl\/fl<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Abcg1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>fl\/fl<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice with\n              <jats:italic>Myh11Cre<\/jats:italic>\n              <jats:sup>\n                <jats:italic>ERT2<\/jats:italic>\n              <\/jats:sup>\n              transgenic mice. To induce SMC cholesterol accumulation and atherogenesis, we fed\n              <jats:italic>Myh11Cre<\/jats:italic>\n              <jats:sup>\n                <jats:italic>ERT2<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Abca1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>fl\/fl<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Abcg1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>fl\/fl<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              ,\n              <jats:italic>Myh11Cre<\/jats:italic>\n              <jats:sup>\n                <jats:italic>ERT2<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Abca1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>fl\/fl<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              ,\n              <jats:italic>Myh11Cre<\/jats:italic>\n              <jats:sup>\n                <jats:italic>ERT2<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Abcg1<\/jats:italic>\n              <jats:sup>\n                <jats:italic>fl\/fl<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              , and\n              <jats:italic>Myh11Cre<\/jats:italic>\n              <jats:sup>\n                <jats:italic>ERT2<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>Ldlr<\/jats:italic>\n              <jats:sup>\n                <jats:italic>\u2212\/\u2212<\/jats:italic>\n              <\/jats:sup>\n              mice Western-type diet for 16 weeks.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Combined\n              <jats:italic>SMC-Abca1\/Abcg1<\/jats:italic>\n              deficiency increased vasoconstriction in aortic rings induced by the \u03b1\n              <jats:sub>1<\/jats:sub>\n              -AR agonist phenylephrine. Unexpectedly,\n              <jats:italic>SMC-Abca1\/Abcg1<\/jats:italic>\n              deficiency induced urinary bladder distension by &gt;20-fold. This was reversed by the \u03b1\n              <jats:sub>1<\/jats:sub>\n              -AR antagonist tamsulosin, indicating its dependence on bladder neck SMC constriction. Moreover,\n              <jats:italic>SMC-Abca1\/Abcg1<\/jats:italic>\n              deficiency decreased contractile markers and increased macrophage and fibroblast markers in bladder SMCs, indicating SMC transdifferentiation. This was accompanied by free cholesterol accumulation and increased endoplasmic reticulum stress.\n              <jats:italic>SMC-Abca1\/Abcg1<\/jats:italic>\n              deficiency did not induce thoracic aorta SMC transdifferentiation, presumably due to increased cholesteryl ester accumulation and no endoplasmic reticulum stress in thoracic aorta SMCs. Surprisingly,\n              <jats:italic>SMC-Abca1\/Abcg1<\/jats:italic>\n              deficiency did not affect atherosclerotic lesion size or composition in the aortic root or brachiocephalic artery.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              We uncover a new role of SMC cholesterol efflux pathways in suppressing \u03b1\n              <jats:sub>1<\/jats:sub>\n              -AR\u2013mediated vasoconstriction and bladder SMC transdifferentiation, decreasing urinary bladder distension. Our data may provide a mechanistic link for the association between urinary bladder distension and diabetes in humans, particularly because diabetes is associated with decreased cholesterol efflux.\n              <jats:italic>SMC-Abca1\/Abcg1<\/jats:italic>\n              deficiency did not affect atherosclerotic lesion size or plaque composition, presumably due to low expression of\n              <jats:italic>Abca1\/Abcg1<\/jats:italic>\n              in intimal SMCs.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.124.325103","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T10:00:29Z","timestamp":1739268029000},"page":"491-507","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["SMC Abca1 and Abcg1 Deficiency Enhances Urinary Bladder Distension but Not Atherosclerosis"],"prefix":"10.1161","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6010-5096","authenticated-orcid":true,"given":"Benedek","family":"Halmos","sequence":"first","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anouk M.","family":"La Rose","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9827-5307","authenticated-orcid":true,"given":"Daisey","family":"Methorst","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-8701","authenticated-orcid":true,"given":"Anouk G.","family":"Groenen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0900-0130","authenticated-orcid":true,"given":"Dalibor","family":"Nakl\u00e1dal","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology (D.N., A.v.B., H.B., L.E.D., R.H.H.), University Medical Center Groningen, University of Groningen, the Netherlands."},{"name":"Comenius University Science Park, Bratislava, Slovakia (D.N.)."},{"name":"5th Department of Internal Medicine, Faculty of Medicine, Comenius University Bratislava, Slovakia (D.N.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Venetia","family":"Bazioti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6312-3321","authenticated-orcid":true,"given":"Mirjam H.","family":"Koster","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5500-3282","authenticated-orcid":true,"given":"Niels J.","family":"Kloosterhuis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azuwerus van","family":"Buiten","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology (D.N., A.v.B., H.B., L.E.D., R.H.H.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-5345","authenticated-orcid":true,"given":"Elisabeth M.","family":"Schouten","sequence":"additional","affiliation":[{"name":"Department of Cardiology (E.M.S.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolette C.A.","family":"Huijkman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3559-2516","authenticated-orcid":true,"given":"Miriam","family":"Langelaar-Makkinje","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8942-6048","authenticated-orcid":true,"given":"Laura","family":"Bongiovanni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."},{"name":"Department of Biomolecular Health Sciences, Dutch Molecular Pathology Center, University of Utrecht, the Netherlands (L.B., S.M.D.N., A.d.B.)."},{"name":"Department of Veterinary Medicine, University of Teramo, Italy (L.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5348-4541","authenticated-orcid":true,"given":"Simon M.","family":"De Neck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."},{"name":"Department of Biomolecular Health Sciences, Dutch Molecular Pathology Center, University of Utrecht, the Netherlands (L.B., S.M.D.N., A.d.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8579-2649","authenticated-orcid":true,"given":"Alain","family":"de Bruin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."},{"name":"Department of Biomolecular Health Sciences, Dutch Molecular Pathology Center, University of Utrecht, the Netherlands (L.B., S.M.D.N., A.d.B.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik","family":"Buikema","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology (D.N., A.v.B., H.B., L.E.D., R.H.H.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-8353","authenticated-orcid":true,"given":"Leo E.","family":"Deelman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology (D.N., A.v.B., H.B., L.E.D., R.H.H.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6985-7107","authenticated-orcid":true,"given":"Marius C.","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Department of Pathology (M.C.v.d.H.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2518-737X","authenticated-orcid":true,"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (B.H., A.M.L.R., D.M., A.G.G., V.B., M.H.K., N.J.K., N.C.A.H., M.L.-M., L.B., S.M.D.N., A.d.B., F.K., M.W.), University Medical Center Groningen, University of Groningen, the Netherlands."},{"name":"Department of Laboratory Medicine (F.K.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3444-5548","authenticated-orcid":true,"given":"Igle Jan","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Urology (I.J.d.J.), University Medical Center Groningen, University of Groningen, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-4582","authenticated-orcid":true,"given":"Judith C.","family":"Sluimer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, the Netherlands (J.C.S.)."},{"name":"Department of Medical Clinic II for Kidney and Hypertension Diseases, Rheumatological and Immunological Diseases, Rheinisch-Westf\u00e4lische Technische Hochschule (RWTH) Aachen, Germany (J.C.S.)."},{"name":"British Heart Foundation (BHF) Centre for Cardiovascular Sciences, University 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