RhoA/Rho-kinase signaling

A therapeutic target in pulmonary hypertension

Scott A Barman, Shu Zhu, Richard E. White

Research output: Contribution to journalReview article

44 Citations (Scopus)

Abstract

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of the pulmonary vasculature. Both animal and clinical studies suggest that ROCK inhibitors are effective for treatment of severe PAH with minimal risk, which supports the premise that ROCKs are important therapeutic targets in pulmonary hypertension and that ROCK inhibitors are a promising new class of drugs for this devastating disease.

Original languageEnglish (US)
Pages (from-to)663-671
Number of pages9
JournalVascular Health and Risk Management
Volume5
StatePublished - Dec 1 2009

Fingerprint

rho-Associated Kinases
Pulmonary Hypertension
Lung
Myosin-Light-Chain Phosphatase
Inflammation
Monomeric GTP-Binding Proteins
Therapeutics
Muscle Contraction
Vasoconstriction
Constriction
Vascular Resistance
Muscle Cells
Blood Vessels
Arterial Pressure
Animal Models
Cell Proliferation
Pharmaceutical Preparations

Keywords

  • Fasudil
  • Pulmonary arterial hypertension
  • Rho-kinase
  • Vasoconstriction

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hematology
  • Public Health, Environmental and Occupational Health
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

RhoA/Rho-kinase signaling : A therapeutic target in pulmonary hypertension. / Barman, Scott A; Zhu, Shu; White, Richard E.

In: Vascular Health and Risk Management, Vol. 5, 01.12.2009, p. 663-671.

Research output: Contribution to journalReview article

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N2 - Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling as well as inflammation. Rho-kinases (ROCKs) are one of the best-described effectors of the small G-protein RhoA, and ROCKs are involved in a variety of cellular functions including muscle cell contraction, proliferation and vascular inflammation through inhibition of myosin light chain phosphatase and activation of downstream mediators. A plethora of evidence in animal models suggests that heightened RhoA/ROCK signaling is important in the pathogenesis of pulmonary hypertension by causing enhanced constriction and remodeling of the pulmonary vasculature. Both animal and clinical studies suggest that ROCK inhibitors are effective for treatment of severe PAH with minimal risk, which supports the premise that ROCKs are important therapeutic targets in pulmonary hypertension and that ROCK inhibitors are a promising new class of drugs for this devastating disease.

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