Abstract
The small GTP-binding protein, RhoA, and its downstream effector protein, rho-kinase, have been implicated in the pathogenesis of a number of cardiovascular diseases. The activation of rho-kinase is involved in the development of increased vascular tone, endothelial dysfunction, inflammation, and restenosis; and that the inhibition of rho-kinase has been shown to have a beneficial effect in a variety of cardiovascular disorders. It is our hypothesis that rho-kinase inhibitors promote vasodilation independent of the mechanism that increases vasoconstrictor tone and moreover, the RhoA/rho-kinase pathway has a role in the regulation of smooth muscle tone under physiological conditions. The objective of this review is to improve our current understanding of the role of RhoA/rho-kinase pathway in the regulation of vasoconstrictor tone and the use of rho-kinase inhibitors in the treatment of cardiovascular disorders with an emphasis on pulmonary hypertension.
Keywords: Intracellular signaling peptides and proteins, protein kinases, RhoA/rho-kinase pathway, muscle, smooth, vascular, pulmonary hypertension, pulmonary vascular bed, systemic vascular bed, signal transduction, inhibitors/pharmacology, cardiovascular diseases, fasudil, HA-1077, Y-27632
Current Drug Discovery Technologies
Title: The Role of the RhoA/rho-kinase Pathway in Pulmonary Hypertension
Volume: 6 Issue: 1
Author(s): Bobby D. Nossaman and Philip J. Kadowitz
Affiliation:
Keywords: Intracellular signaling peptides and proteins, protein kinases, RhoA/rho-kinase pathway, muscle, smooth, vascular, pulmonary hypertension, pulmonary vascular bed, systemic vascular bed, signal transduction, inhibitors/pharmacology, cardiovascular diseases, fasudil, HA-1077, Y-27632
Abstract: The small GTP-binding protein, RhoA, and its downstream effector protein, rho-kinase, have been implicated in the pathogenesis of a number of cardiovascular diseases. The activation of rho-kinase is involved in the development of increased vascular tone, endothelial dysfunction, inflammation, and restenosis; and that the inhibition of rho-kinase has been shown to have a beneficial effect in a variety of cardiovascular disorders. It is our hypothesis that rho-kinase inhibitors promote vasodilation independent of the mechanism that increases vasoconstrictor tone and moreover, the RhoA/rho-kinase pathway has a role in the regulation of smooth muscle tone under physiological conditions. The objective of this review is to improve our current understanding of the role of RhoA/rho-kinase pathway in the regulation of vasoconstrictor tone and the use of rho-kinase inhibitors in the treatment of cardiovascular disorders with an emphasis on pulmonary hypertension.
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Cite this article as:
Nossaman D. Bobby and Kadowitz J. Philip, The Role of the RhoA/rho-kinase Pathway in Pulmonary Hypertension, Current Drug Discovery Technologies 2009; 6 (1) . https://dx.doi.org/10.2174/157016309787581057
DOI https://dx.doi.org/10.2174/157016309787581057 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
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