{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:25:45Z","timestamp":1784921145744,"version":"3.55.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,12,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Kruppel\u2010like factor 2 (\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2) is an important zinc\u2010finger transcription factor that maintains endothelial homeostasis by its anti\u2010inflammatory, \u2010thrombotic, \u2010oxidative, and \u2010proliferative effects in endothelial cells. In light of the potent vasoprotective effects of\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2, modulating\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 expression or function could give rise to new therapeutic strategies to treat cardiovascular diseases.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              High\u2010throughput drug screening based on\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 promoter luciferase reporter assay was performed to screen\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 activators. Real\u2010time\n              <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n              and western blot were used to detect gene and protein expression. Identified\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 activator was orally administered to ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice to evaluate anti\u2010atherosclerotic efficacy. By screening 2400 compounds in the Spectrum library, we identified suberanilohydroxamic (SAHA) acid, also known as vorinostat as a pharmacological\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 activator through myocyte enhancer factor 2. We found that\n              <jats:styled-content style=\"fixed-case\">SAHA<\/jats:styled-content>\n              exhibited anti\u2010inflammatory effects and attenuated monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha. We further showed that the inhibitory effect of\n              <jats:styled-content style=\"fixed-case\">SAHA<\/jats:styled-content>\n              on endothelial inflammation and ensuing monocyte adhesion was\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 dependent using\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2\u2010deficient mouse lung endothelial cells or\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 small interfering\n              <jats:styled-content style=\"fixed-case\">RNA\u2013<\/jats:styled-content>\n              depleted human endothelial cells. Importantly, we observed that oral administration of\n              <jats:styled-content style=\"fixed-case\">SAHA<\/jats:styled-content>\n              reduced diet\u2010induced atherosclerotic lesion development in ApoE\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice without significant effect on serum lipid levels.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These results demonstrate that\n              <jats:styled-content style=\"fixed-case\">SAHA<\/jats:styled-content>\n              has\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2\u2010dependent anti\u2010inflammatory effects in endothelial cells and provide the proof of concept that\n              <jats:styled-content style=\"fixed-case\">KLF<\/jats:styled-content>\n              2 activation could be a promising therapeutic strategy for treating atherosclerosis.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.007134","type":"journal-article","created":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T01:10:13Z","timestamp":1512090613000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":55,"title":["Suberanilohydroxamic Acid as a Pharmacological Kruppel\u2010Like Factor 2 Activator That Represses Vascular Inflammation and Atherosclerosis"],"prefix":"10.1161","volume":"6","author":[{"given":"Yanni","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY"},{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 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