{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:50:45Z","timestamp":1788828645474,"version":"build-2803163510"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2015,3,3]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Oxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase\u2013derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element\u2013binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>Using cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II\u2013infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Kr\u00fcppel-like factor 2, and Kr\u00fcppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell\u2013specific SREBP2 transgenic mice, locked nucleic acid\u2013modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II\u2013induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell\u2013dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1\u03b2.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our findings suggest that SREBP2\u2013miR-92a\u2013inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.114.013675","type":"journal-article","created":{"date-parts":[[2014,12,31]],"date-time":"2014-12-31T03:23:59Z","timestamp":1419996239000},"page":"805-814","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":145,"title":["Oxidative Stress Activates Endothelial Innate Immunity via Sterol Regulatory Element Binding Protein 2 (SREBP2) Transactivation of MicroRNA-92a"],"prefix":"10.1161","volume":"131","author":[{"given":"Zhen","family":"Chen","sequence":"first","affiliation":[{"name":"From Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wen","sequence":"additional","affiliation":[{"name":"From Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcy","family":"Martin","sequence":"additional","affiliation":[{"name":"From Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Yi","family":"Hsu","sequence":"additional","affiliation":[{"name":"From Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhou","family":"Fang","sequence":"additional","affiliation":[{"name":"From Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei 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Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei Veterans..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKenna J.","family":"Geary","sequence":"additional","affiliation":[{"name":"From Department of Medicine, School of Medicine (Z.C., L.W., M.M., L.F., T.-Y.L., M.J.C., Y.I.M., J.Y.-J.S.) and Department of Bioengineering (S.C.), University of California, San Diego; Department of Cardiovascular Sciences, Houston Methodist Medical Institute, Houston (L.F.); Biochemistry and Molecular Biology Graduate Program (M.M.) and Division of Biomedical Sciences, School of Medicine (D.A.J.), University of California, Riverside; Division of Cardiology, Department of Medicine, Taipei 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