BACKGROUND: Liver-X-receptors, LXRa ( @entity23710 ) and @entity24725 ( @entity24725 ), encode 2 different but highly homologous isoforms of transcription factors belonging to the nuclear receptor superfamily. Whether LXRa and @entity24725 subtypes have discrete roles in the regulation of cardiac physiology/pathology is unknown. We determine the role of each @entity24725 subtype in @entity741 /reperfusion (MI/R) injury. METHODS AND RESULTS: @entity19 (wild type; those genetically depleted of LXRa, @entity24725 , or both; and those overexpressing LXRa or @entity24725 by in vivo intramyocardial adenoviral vector) were subjected to MI/R injury. Both LXRa and @entity24725 were detected in wild-type @entity19 heart. LXRa, but not @entity24725 , was significantly upregulated after MI/R. Dual activation of LXRa and @entity24725 by natural and synthetic agonists reduced @entity583 and improved contractile function after MI/R. Mechanistically, @entity24725 activation inhibited MI/R-induced oxidative stress and nitrative stress, attenuated @entity2383 , and reduced cardiomyocyte apoptosis in @entity63 /reperfused myocardium. The aforementioned cardioprotective effects of @entity24725 agonists were impaired in the setting of cardiac-specific gene silencing of LXRa, but not @entity24725 subtype. Moreover, LXRa/b double-knockout and LXRa-knockout @entity19 , but not @entity24725 -knockout @entity19 , increased MI/R injury, exacerbated MI/R-induced oxidative/nitrative stress, and aggravated @entity2383 . Furthermore, cardiac LXRa, not @entity24725 , overexpression via adenoviral transfection suppressed MI/R injury. CONCLUSIONS: Our study provides the first direct evidence that the LXRa, but not @entity24725 , subtype is a novel endogenous cardiac protective receptor against MI/R injury. Drug development strategies specifically targeting LXRa may be beneficial in treating @entity741 .

Activation of liver-X-receptor a but not liver-X-receptor b protects against XXXX /reperfusion injury.

@entity63 :: ('MESH:D007511', 'Disease') :: ['ischemic'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse', 'Mice'] @entity23710 :: ('22259(Tax:10090)', 'Gene') :: ['NR1H3'] @entity24725 :: ('22260(Tax:10090)', 'Gene') :: ['LXRb', 'LXR', 'NR1H2'] @entity741 :: ('MESH:D017202', 'Disease') :: ['myocardial ischemia', 'ischemic heart disease'] @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['endoplasmic reticulum stress and mitochondrial dysfunction']
@entity741 :: (MESH:D017202,Disease) :: ['myocardial ischemia']
