{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:16:48Z","timestamp":1790997408572,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,5,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Liver X receptor (LXR) belongs to the metabolic nuclear receptor superfamily, which plays a critical regulatory role in vascular physiology\/pathology. However, effects of systemic LXR activation on established vulnerable plaques and the potential isotype\u2010specific role involved remain unclear.<\/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              The 8\u2010week\u2010old male apolipoprotein E\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice went through carotid branch ligation and renal artery constriction, combined with a high\u2010fat diet. Plaques in the left carotid artery acquired vulnerable features 4\u00a0weeks later, confirmed by magnetic resonance imaging scans and histological analysis. From that time on, mice were injected intraperitoneally daily with PBS or GW3965 (10\u00a0mg\/kg per day) for an additional 4\u00a0weeks. Treatment with LXR agonists reduced the lesion volume by 52.61%, compared with the vehicle group. More important, a profile of less intraplaque hemorrhage detection and necrotic core formation was found. These actions collectively attenuated the incidence of plaque rupture. Mechanistically, reduced lesional apoptosis, enhanced efferocytosis, and alleviated endoplasmic reticulum stress are involved in the process. Furthermore, genetic ablation of LXR\u03b1, but not LXR\u03b2, blunted the protective effects of LXR on the endoplasmic reticulum stress\u2013elicited C\/EBP\u2010homologous protein pathway in peritoneal macrophages. In concert with the LXR\u03b1\u2010predominant role in vitro, activated LXR failed to stabilize vulnerable plaques and correct the acquired cellular anomalies in LXR\u03b1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              apolipoprotein E\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our results revealed that LXR\u03b1 mediates the capacity of LXR activation to stabilize vulnerable plaques and prevent plaque rupture via amelioration of macrophage endoplasmic reticulum stress, lesional apoptosis, and defective efferocytosis. These findings might expand the application scenarios of LXR therapeutics for atherosclerosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.018455","type":"journal-article","created":{"date-parts":[[2021,5,8]],"date-time":"2021-05-08T09:01:41Z","timestamp":1620464501000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Protective Functions of Liver X Receptor \u03b1 in Established Vulnerable Plaques: Involvement of Regulating Endoplasmic Reticulum\u2013Mediated Macrophage Apoptosis and Efferocytosis"],"prefix":"10.1161","volume":"10","author":[{"given":"Xinyu","family":"Che","sequence":"first","affiliation":[{"name":"Department of Cardiology Renji Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renji Hospital School 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