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Protease-activated receptor-1 contributes to cardiac remodeling and hypertrophy

Rafal Pawlinski1, Michael Tencati, Craig R Hampton

  • 1The Scripps Research Institute, Department of Immunology, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.

Circulation
|October 31, 2007
PubMed

Insights

Protease-activated receptor-1 (PAR-1) deficiency improves cardiac function after heart injury by reducing left ventricle dilation. However, PAR-1 deficiency did not affect infarct size, while its overexpression induced eccentric hypertrophy.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Thrombosis Research

Background:

  • Protease-activated receptor-1 (PAR-1) is a receptor for thrombin, expressed in cardiac cells like cardiomyocytes and fibroblasts.
  • PAR-1 signaling is implicated in cardiomyocyte hypertrophy and fibroblast proliferation.
  • Tissue factor (TF) and thrombin are known contributors to cardiac ischemia-reperfusion (I/R) injury.

Purpose of the Study:

  • To investigate the role of PAR-1 in cardiac infarction, remodeling, and hypertrophy following I/R injury.
  • To analyze the effects of cardiomyocyte-specific PAR-1 overexpression on cardiac function and structure.

Main Methods:

  • Utilized PAR-1 deficient (PAR-1-/-) and wild-type mice subjected to cardiac I/R injury.
  • Investigated cardiac remodeling and function using echocardiography and histological analysis.
  • Examined the impact of cardiomyocyte-specific PAR-1 overexpression and TF gene deletion.

Main Results:

  • PAR-1 deficiency attenuated left ventricular dilation and improved cardiac function 2 weeks post-I/R injury.
  • PAR-1 deficiency did not alter infarct size but increased ERK1/2 activation in injured areas.
  • Cardiomyocyte-specific PAR-1 overexpression led to eccentric hypertrophy and dilated cardiomyopathy, which was reduced by deleting the TF gene in cardiomyocytes.

Conclusions:

  • PAR-1 plays a significant role in cardiac remodeling and hypertrophy post-myocardial infarction.
  • Overexpression of PAR-1 in cardiomyocytes induces eccentric hypertrophy, suggesting a mechanism for dilated cardiomyopathy.
  • Targeting PAR-1 may offer a novel therapeutic strategy for reducing cardiac hypertrophy and heart failure after myocardial infarction.
Abstract

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