title: SWI/SNF chromatin remodeling enzymes are associated with cardiac hypertrophy in a genetic rat model of hypertension.
abstract: Pathological cardiac hypertrophy is characterized by a sustained increase in cardiomyocyte size and re-activation of the fetal cardiac gene program. Previous studies implicated SWI/SNF chromatin remodeling enzymes as regulators of the fetal cardiac gene program in surgical models of cardiac hypertrophy. Although hypertension is a common risk factor for developing cardiac hypertrophy, there has not yet been any investigation into the role of SWI/SNF enzymes in cardiac hypertrophy using genetic models of hypertension. In this study, we tested the hypothesis that components of the SWI/SNF complex are activated and recruited to promoters that regulate the fetal cardiac gene program in hearts that become hypertrophic as a result of salt induced hypertension. Utilizing the Dahl salt-sensitive (S) rat model, we found that the protein levels of several SWI/SNF subunits required for heart development, Brg1, Baf180, and Baf60c, are elevated in hypertrophic hearts from S rats fed a high salt diet compared with normotensive hearts from Dahl salt-resistant (R) rats fed the same diet. Furthermore, we detected significantly higher levels of SWI/SNF subunit enrichment as well as evidence of more accessible chromatin structure on two fetal cardiac gene promoters in hearts from S rats compared with R rats. Our data implicate SWI/SNF chromatin remodeling enzymes as regulators of gene expression in cardiac hypertrophy resulting from salt induced hypertension. Thus we provide novel insights into the epigenetic mechanisms by which salt induced hypertension leads to cardiac hypertrophy.
authors.affiliation: Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH.
authors.forename: Aanchal
authors.initials: A
authors.lastname: Mehrotra
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.forename: Ivana L
authors.initials: IL
authors.lastname: de la Serna
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000503:physiopathology*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D011401:Promoter Regions, Genetic; D051381:Rats; D020303:Rats, Inbred Dahl / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C445179:SWI-SNF-B chromatin-remodeling complex; D017673:Sodium Chloride, Dietary; D014157:Transcription Factors