{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:16:12Z","timestamp":1791000972228,"version":"4.1.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2022,3,18]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Metabolic syndrome is related to cardiovascular diseases, which is attributed in part, to arterial stiffness; however, the mechanisms remain unclear. The present study aimed to investigate the molecular mechanisms of metabolic syndrome\u2013induced arterial stiffness and to identify new therapeutic targets.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Arterial stiffness was induced by high-fat\/high-sucrose diet in mice, which was quantified by Doppler ultrasound. Four-dimensional label-free quantitative proteomic analysis, affinity purification and mass spectrometry, and immunoprecipitation and GST (glutathione S-transferase) pull-down experiments were performed to explore the mechanism of YAP (Yes-associated protein)-mediated TGF (transforming growth factor) \u03b2 pathway activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              YAP protein was upregulated in the aortic tunica media of mice fed a high-fat\/high-sucrose diet for 2 weeks and precedes arterial stiffness. Smooth muscle cell\u2013specific YAP knockdown attenuated high-fat\/high-sucrose diet\u2013induced arterial stiffness and activation of TGF\u03b2-Smad2\/3 signaling pathway in arteries. By contrast,\n              <jats:italic>Myh11Cre<\/jats:italic>\n              <jats:sup>\n                <jats:italic>ERT2<\/jats:italic>\n              <\/jats:sup>\n              <jats:italic>-Yap<\/jats:italic>\n              <jats:sup>\n                <jats:italic>Tg<\/jats:italic>\n              <\/jats:sup>\n              mice exhibited exacerbated high-fat\/high-sucrose diet\u2013induced arterial stiffness and enhanced TGF\u03b2-activated Smad2\/3 phosphorylation in arteries. PPM1B (protein phosphatase, Mg\n              <jats:sup>2+<\/jats:sup>\n              \/Mn\n              <jats:sup>2+<\/jats:sup>\n              -dependent 1B) was identified as a YAP-bound phosphatase that translocates into the nucleus to dephosphorylate Smads (mothers against decapentaplegic homologs) in response to TGF\u03b2. This process was inhibited by YAP through removal of the K63-linked ubiquitin chain of PPM1B at K326.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>This study provides a new mechanism by which smooth muscle cell YAP regulates the TGF\u03b2 pathway and a potential therapeutic target in metabolic syndrome\u2013associated arterial stiffness.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.121.320464","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T10:00:13Z","timestamp":1645178413000},"page":"851-867","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Yes-Associated Protein Targets the Transforming Growth Factor \u03b2 Pathway to Mediate High-Fat\/High-Sucrose Diet-induced Arterial Stiffness"],"prefix":"10.1161","volume":"130","author":[{"given":"Yanan","family":"Liu","sequence":"first","affiliation":[{"name":"Tianjin Institute of Cardiology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Second Hospital of Tianjin Medical University (Y.L., X.L., D.A.), Tianjin Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengke","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology (M.L., Y.Z., D.A.), Tianjin Medical University, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Lv","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Cardiology, The Province and Ministry Co-sponsored Collaborative 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