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Updated: May 1, 2026
Single Cell Transcriptional Profiling of Adult Mouse Cardiomyocytes
Published on: December 28, 2011
Whole-genome profiling highlights the molecular complexity underlying eccentric cardiac hypertrophy
Justin Barnes1, Betty Pat2, Yuan-Wen Chen2
1Department 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.
Insights
Eccentric cardiac remodeling from volume overload (VO) involves complex gene expression changes in matrix, metabolism, and contractile function, unlike concentric remodeling from pressure overload (PO). This highlights new therapeutic targets for heart failure prevention.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cardiac Remodeling
Background:
- Heart failure often follows myocardial hypertrophy and remodeling.
- Concentric remodeling results from pressure overload (PO), while eccentric remodeling stems from volume overload (VO).
- Distinct molecular mechanisms drive these different hypertrophy patterns, necessitating further elucidation.
Purpose of the Study:
- Identify novel therapeutic targets for cardiovascular conditions.
- Focus on hypertrophy resistant to current medical treatments, particularly pure VO.
- Elucidate molecular mechanisms underlying eccentric vs. concentric cardiac remodeling.
Main Methods:
- Induced concentric (TAC) and eccentric (ACF) hypertrophy in rat models.
- Assessed left ventricular (LV) hypertrophy and function via hemodynamic and echocardiographic analyses.
- Analyzed gene expression changes using microarray and Ingenuity Pathway Analysis.
Main Results:
- Both TAC and ACF models increased LV mass; TAC caused concentric, ACF caused eccentric remodeling.
- Eccentric remodeling showed more extensive gene expression alterations than concentric remodeling.
- VO led to activation of matrix and cell cycle genes, downregulation of oxidative metabolism genes, and contractile dysfunction gene dysregulation.
Conclusions:
- Eccentric remodeling is a more complex process than concentric remodeling.
- Early VO involves critical changes in matrix regulation, metabolism, cell proliferation, and cardiac function.
- Findings provide insights for developing new treatments to prevent VO-induced heart failure progression.
Objectives:
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.
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