Rho kinases and cardiac remodeling

Toru Shimizu, James K. Liao

Research output: Contribution to journalReview articlepeer-review

39 Citations (Scopus)

Abstract

Hypertensive cardiac remodeling is characterized by left ventricular hypertrophy and interstitial fibrosis, which can lead to heart failure with preserved ejection fraction. The Rho-associated coiled-coil containing kinases (ROCKs) are members of the serine/threonine protein kinase family, which mediates the downstream effects of the small GTP-binding protein RhoA. There are 2 isoforms: ROCK1 and ROCK2. They have different functions in different types of cells and tissues. There is growing evidence that ROCKs contribute to the development of cardiovascular diseases, including cardiac fibrosis, hypertrophy, and subsequent heart failure. Recent experimental studies using ROCK inhibitors, such as fasudil, have shown the benefits of ROCK inhibition in cardiac remodeling. Mice lacking each ROCK isoform also exhibit reduced myocardial fibrosis in a variety of pathological models of cardiac remodeling. Indeed, clinical studies with fasudil have suggested that ROCKs could be potential novel therapeutic targets for cardiovascular diseases. In this review, we summarize the current understanding of the roles of ROCKs in the development of cardiac fibrosis and hypertrophy and discuss their therapeutic potential for deleterious cardiac remodeling.

Original languageEnglish
Pages (from-to)1491-1498
Number of pages8
JournalCirculation Journal
Volume80
Issue number7
DOIs
Publication statusPublished - 2016

Keywords

  • Fibrosis
  • Heart diseases
  • Heart failure
  • Hypertrophy
  • Ventricular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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