{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T03:48:13Z","timestamp":1793936893855,"version":"4.8.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Liver-X-receptors, LXR\u03b1 (NR1H3) and LXR\u03b2 (NR1H2), encode 2 different but highly homologous isoforms of transcription factors belonging to the nuclear receptor superfamily. Whether LXR\u03b1 and LXR\u03b2 subtypes have discrete roles in the regulation of cardiac physiology\/pathology is unknown. We determine the role of each LXR subtype in myocardial ischemia\/reperfusion (MI\/R) injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>Mice (wild type; those genetically depleted of LXR\u03b1, LXR\u03b2, or both; and those overexpressing LXR\u03b1 or LXR\u03b2 by in vivo intramyocardial adenoviral vector) were subjected to MI\/R injury. Both LXR\u03b1 and LXR\u03b2 were detected in wild-type mouse heart. LXR\u03b1, but not LXR\u03b2, was significantly upregulated after MI\/R. Dual activation of LXR\u03b1 and LXR\u03b2 by natural and synthetic agonists reduced myocardial infarction and improved contractile function after MI\/R. Mechanistically, LXR activation inhibited MI\/R-induced oxidative stress and nitrative stress, attenuated endoplasmic reticulum stress and mitochondrial dysfunction, and reduced cardiomyocyte apoptosis in ischemic\/reperfused myocardium. The aforementioned cardioprotective effects of LXR agonists were impaired in the setting of cardiac-specific gene silencing of LXR\u03b1, but not LXR\u03b2 subtype. Moreover, LXR\u03b1\/\u03b2 double-knockout and LXR\u03b1-knockout mice, but not LXR\u03b2-knockout mice, increased MI\/R injury, exacerbated MI\/R-induced oxidative\/nitrative stress, and aggravated endoplasmic reticulum stress and mitochondrial dysfunction. Furthermore, cardiac LXR\u03b1, not LXR\u03b2, overexpression via adenoviral transfection suppressed MI\/R injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our study provides the first direct evidence that the LXR\u03b1, but not LXR\u03b2, subtype is a novel endogenous cardiac protective receptor against MI\/R injury. Drug development strategies specifically targeting LXR\u03b1 may be beneficial in treating ischemic heart disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.114.001260","type":"journal-article","created":{"date-parts":[[2014,10,3]],"date-time":"2014-10-03T02:00:51Z","timestamp":1412301651000},"page":"1032-1041","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["Activation of Liver-X-Receptor \u03b1 But Not Liver-X-Receptor \u03b2 Protects Against Myocardial Ischemia\/Reperfusion Injury"],"prefix":"10.1161","volume":"7","author":[{"given":"Qing","family":"He","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Pu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancai","family":"Yuan","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne Bond","family":"Lau","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Liang","family":"Ma","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"He","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China (Q.H., J.P., A.Y., B.H.); Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., X.-L.M.); and Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA (E.G., W.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr387"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.02.576"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2010.010210"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.08.074"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq496"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs011"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3312"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.12.024"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M900096-JLR200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31909"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp180"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq109"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0323-z"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.782300"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2010.7"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.02.011"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-011-0155-2"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.10.7025"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806974105"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00184.2009"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00553.2009"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-306142"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2010.07.003"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00517.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0609438"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-11-19"},{"key":"e_1_3_3_28_2","first-page":"3007","article-title":"LXR agonists and ABCG1-dependent cholesterol efflux in MCF-7 breast cancer cells: relation to proliferation and apoptosis.","volume":"32","author":"El Roz A","year":"2012","unstructured":"El Roz A, Bard JM, Huvelin JM, Nazih H. 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