{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:04:23Z","timestamp":1792782263569,"version":"4.5.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T00:00:00Z","timestamp":1423612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Netherlands Heart Foundation","award":["2007\u2009T046"],"award-info":[{"award-number":["2007\u2009T046"]}]},{"DOI":"10.13039\/501100003246","name":"NWO","doi-asserted-by":"publisher","award":["VENI 916.10.117"],"award-info":[{"award-number":["VENI 916.10.117"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"NWO","doi-asserted-by":"publisher","award":["VIDI 917.13.350"],"award-info":[{"award-number":["VIDI 917.13.350"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Liver X receptors (LXRs) transcriptionally regulate inflammation, metabolism, and immunity. Synthetic LXR agonists have been evaluated for their efficacy in the cardiovascular system; however, they elicit prolipogenic side effects which substantially limit their therapeutic use. AZ876 is a novel high-affinity LXR agonist. Herein, we aimed to determine the cardioprotective potential of LXR activation with AZ876.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Cardiac hypertrophy was induced in C57Bl6\/J mice via transverse aortic constriction (TAC) for 6 weeks. During this period, mice received chow supplemented or not with AZ876 (20\u2009\u00b5mol\/kg\/day). In murine hearts, LXR\u03b1 protein expression was up-regulated \u223c7-fold in response to TAC. LXR activation with AZ876 attenuated this increase, and significantly reduced TAC-induced increases in heart weight, myocardial fibrosis, and cardiac dysfunction without affecting blood pressure. At the molecular level, AZ876 suppressed up-regulation of hypertrophy- and fibrosis-related genes, and further inhibited prohypertrophic and profibrotic transforming growth factor \u03b2 (TGF\u03b2)\u2013Smad2\/3 signalling. In isolated cardiac myocytes and fibroblasts, immunocytochemistry confirmed nuclear expression of LXR\u03b1 in both these cell types. In cardiomyocytes, phenylephrine-stimulated cellular hypertrophy was significantly decreased in AZ876-treated cells. In cardiac fibroblasts, AZ876 prevented TGF\u03b2- and angiotensin II-induced fibroblast collagen synthesis, and inhibited up-regulation of the myofibroblastic marker, \u03b1-smooth muscle actin. Plasma triglycerides and liver weight were unaltered following AZ876 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AZ876 activation of LXR protects from adverse cardiac remodelling in pathological pressure overload, independently of blood pressure. LXR may thus represent a putative molecular target for antihypertrophic and antifibrotic therapies in heart failure prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.243","type":"journal-article","created":{"date-parts":[[2015,2,13]],"date-time":"2015-02-13T04:50:27Z","timestamp":1423803027000},"page":"273-282","source":"Crossref","is-referenced-by-count":37,"title":["The liver X Receptor Agonist AZ876 Protects Against Pathological Cardiac Hypertrophy and Fibrosis Without Lipogenic Side Effects"],"prefix":"10.1093","volume":"17","author":[{"given":"Megan V.","family":"Cannon","sequence":"first","affiliation":[{"name":"University Medical Center Groningen, University of Groningen, Department of Cardiology , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjuan","family":"Yu","sequence":"additional","affiliation":[{"name":"University Medical Center Groningen, University of Groningen, Department of 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