{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:30:16Z","timestamp":1791559816481,"version":"4.3.4"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2025,1,31]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>\n              Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat\/high-sucrose diet (HFHSD)\u2013induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg\n              <jats:sup>2+<\/jats:sup>\n              \/Mn\n              <jats:sup>2+<\/jats:sup>\n              \u2013dependent 1B)-lysine 63(K63) deubiquitination. In this study, we aimed to elucidate the role and mechanisms underlying PPM1B deubiquitination in HFHSD-induced arterial stiffness.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Enzymes governing PPM1B deubiquitination were identified through small interfering RNA (siRNA) screening and mass spectrometry. Glutathione S-transferase pull-down, coimmunoprecipitation, protein purification, and immunofluorescence were used to explore the mechanism underlying PPM1B deubiquitination. Doppler ultrasound was used to evaluate HFHSD-induced arterial stiffness in mice, and telemetry was used to record pulsatile (systolic and diastolic) blood pressure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Smooth muscle cell\u2013specific PPM1B overexpression attenuated HFHSD-induced arterial stiffness in mice in a PPM1B-K326-K63\u2013linked polyubiquitination-dependent manner. Mechanistically, ABRO1 (Abraxas brother 1; a core BRCC36 [BRCA1\/BRCA2 (breast cancer type 1\/2)\u2013containing complex subunit 36] isopeptidase complex component) directly bound YAP and underwent liquid-liquid phase separation with YAP and PPM1B in a YAP-dependent manner, which in turn promoted PPM1B deubiquitination. Furthermore, smooth muscle cell\u2013specific\n              <jats:italic>Abro1<\/jats:italic>\n              -knockout mice and\n              <jats:italic>Brcc3<\/jats:italic>\n              -knockout mice showed attenuated HFHSD-induced arterial stiffness and activation of transforming growth factor-\u03b2\u2013Smad (mothers against decapentaplegic homolog) signaling.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>We elucidated the PPM1B deubiquitination mechanisms and highlighted a potential therapeutic target for metabolic syndrome\u2013related arterial stiffness.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.124.325590","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T10:00:24Z","timestamp":1735725624000},"page":"297-314","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-\u03b2 Pathway Activation Promote High-Fat\/High-Sucrose Diet\u2013Induced Arterial Stiffness"],"prefix":"10.1161","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9775-6157","authenticated-orcid":true,"given":"Yanan","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, China (Y.L., M.L., Z.C., K.B., Z.Z., D.A.)."},{"name":"Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, China (Y.L., M.Z., H.W.)."},{"name":"Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Hunan, China (Y.L., Y.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengke","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, China (Y.L., M.L., Z.C., K.B., Z.Z., D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, China (Y.L., M.L., Z.C., K.B., Z.Z., D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, China (Y.L., M.Z., H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7673-7568","authenticated-orcid":true,"given":"Kaiwen","family":"Bao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, China (Y.L., M.L., Z.C., K.B., Z.Z., D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, China (Y.L., M.L., Z.C., K.B., Z.Z., D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-578X","authenticated-orcid":true,"given":"Meng","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pathology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China (M.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6355-5842","authenticated-orcid":true,"given":"Yongping","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, Center of Coronary Circulation, Xiangya Hospital, Central South University, Hunan, China (Y.L., Y.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5992-9904","authenticated-orcid":true,"given":"Ding","family":"Ai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin Medical University, China (Y.L., M.L., Z.C., K.B., Z.Z., D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Institute of Aging Research, School of Basic Medicine Sciences, Hangzhou Normal University, China (Y.L., M.Z., 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