BACKGROUND: MicroRNAs (miRNAs) and histone deacetylases (HDACs) serve a significant role in the pathogenesis of a variety of @entity65 . The transcriptional regulation of miRNAs is poorly understood in @entity1283 . We investigated whether the expression of miR-133a is epigenetically regulated by class I and IIb HDACs during @entity1184 . METHODS AND RESULTS: Transverse aortic constriction (TAC) was performed in @entity2659 @entity19 to induce pressure overload @entity1184 . @entity19 were treated with class I and IIb HDAC inhibitor (HDACi) via drinking water for 2 and 4 weeks post TAC. miRNA expression was determined by real-time polymerase chain reaction. Echocardiography was performed at baseline and post TAC end points for structural and functional assessment. Chromatin immunoprecipitation was used to identify HDACs and transcription factors associated with miR-133a promoter. miR-133a expression was downregulated by 0.7- and 0.5-fold at 2 and 4 weeks post TAC, respectively, when compared with vehicle control (P<0.05). HDAC inhibition prevented this significant decrease 2 weeks post TAC and maintained miR-133a expression near vehicle control levels, which coincided with (1) a decrease in connective tissue growth factor expression, (2) a reduction in @entity299 and left atrium diameter (marker of end-diastolic pressure), suggesting an improvement in diastolic function. Chromatin immunoprecipitation analysis revealed that @entity12231 and @entity30653 are present on the miR-133a enhancer regions. CONCLUSIONS: The results reveal that HDACs play a role in the regulation of pressure overload-induced miR-133a downregulation. This work is the first to provide insight into an epigenetic-miRNA regulatory pathway in pressure overload-induced @entity299 .

HDACs Regulate miR-133a Expression in Pressure Overload-Induced XXXX .

@entity1184 :: ('MESH:D006984', 'Disease') :: ['hypertrophy', 'hypertrophic remodeling'] @entity1283 :: ('MESH:D006332', 'Disease') :: ['cardiac hypertrophy'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mice'] @entity12231 :: ('433759(Tax:10090)', 'Gene') :: ['HDAC1'] @entity2659 :: ('111334(Tax:10090)', 'Gene') :: ['CD1'] @entity299 :: ('MESH:D006331', 'Disease') :: ['cardiac fibrosis'] @entity30653 :: ('15182(Tax:10090)', 'Gene') :: ['HDAC2'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular diseases']
@entity299 :: (MESH:D006331,Disease) :: ['Cardiac Fibrosis']
