title: Whole-genome profiling highlights the molecular complexity underlying eccentric cardiac hypertrophy.
abstract: OBJECTIVE
  Heart failure is typically preceded by myocardial hypertrophy and remodeling, which can be concentric due to pressure overload (PO), or eccentric because of volume overload (VO). The molecular mechanisms that underlie these differing patterns of hypertrophy are distinct and have yet to be fully elucidated. Thus, the goal of this work is to identify novel therapeutic targets for cardiovascular conditions marked by hypertrophy that have previously been resistant to medical treatment, such as a pure VO.
  
  
  METHODS
  Concentric or eccentric hypertrophy was induced in rats for 2 weeks with transverse aortic constriction (TAC) or aortocaval fistula (ACF), respectively. Hemodynamic and echocardiographic analysis were used to assess the development of left ventricular (LV) hypertrophy and functional differences between groups. Changes in gene expression were determined by microarray and further characterized with Ingenuity Pathway Analysis.
  
  
  RESULTS
  Both models of hypertrophy increased LV mass. Rats with TAC demonstrated concentric LV remodeling while rats with ACF exhibited eccentric LV remodeling. Microarray analysis associated eccentric remodeling with a more extensive alteration of gene expression compared with concentric remodeling. Rats with VO had a marked activation of extracellular matrix genes, promotion of cell cycle genes, downregulation of genes associated with oxidative metabolism, and dysregulation of genes critical to cardiac contractile function. Rats with PO demonstrated similar categorical changes, but with the involvement of fewer individual genes.
  
  
  CONCLUSIONS
  Our results indicate that eccentric remodeling is a far more complex process than concentric remodeling. This study highlights the importance of several key biological functions early in the course of VO, including regulation of matrix, metabolism, cell proliferation, and contractile function. Thus, the results of this analysis will inform the ongoing search for new treatments to prevent the progression to heart failure in VO.
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USADepartment of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Barnes
authors.affiliation: Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Pat
authors.affiliation: Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Yuan-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Pamela C
authors.initials: PC
authors.lastname: Powell
authors.affiliation: Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Bradley
authors.affiliation: Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Junying
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Amrit
authors.initials: A
authors.lastname: Karki
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Xiangqin
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Medicine, Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama, USADepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Guichard
authors.affiliation: Birmingham Department of Veteran Affairs, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Chih-Chang
authors.initials: CC
authors.lastname: Wei
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: James
authors.initials: J
authors.lastname: Collawn
authors.affiliation: Birmingham VA Medical Center, Birmingham, AL 35294-2180, USA louis.dellitalia@va.gov.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Dell'Italia
keywords: heart failure; left ventricular function; pressure overload; volume overload