Whole-genome profiling highlights the molecular complexity underlying eccentric cardiac hypertrophy

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.