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Rho-kinase as a Potential Therapeutic Target for the Treatment of Pulmonary Hypertension
- Source :
- Drug News & Perspectives. 19:517
- Publication Year :
- 2006
- Publisher :
- Portico, 2006.
-
Abstract
- Pulmonary hypertension (PH) is a cardiovascular disorder characterized by vasoconstriction and vascular remodeling. Recently, rapidly increasing evidence from various rat models of PH and patients with PH suggest that small GTPase Rho and its downstream effector, Rho-kinase, play a key role in the pathogenesis of PH. Activation of the Rho/Rho-kinase pathway is important for pulmonary endothelial dysfunction, pulmonary vascular smooth muscle cell contractility, proliferation and apoptosis in PH. A greater Rho-kinase expression and an enhanced Rho-kinase activity have been observed in pulmonary arteries of PH rats, such as hypoxia-induced, monocrotaline-induced and genetic spontaneous PH rats. Moreover, Y-27632 or fasudil, the selective Rho-kinase inhibitors, significantly attenuated PH in various pulmonary hypertensive model rats and patients with PH, but did not reduce systemic blood pressure. Therefore, Rho-kinase inhibitors may have therapeutic potential for the treatment of PH.
- Subjects :
- rho-Associated Kinases
Vascular smooth muscle
Chemistry
Hypertension, Pulmonary
Intracellular Signaling Peptides and Proteins
Fasudil
Protein Serine-Threonine Kinases
Pharmacology
medicine.disease
Pulmonary hypertension
Pathogenesis
Apoptosis
medicine
Animals
Humans
medicine.symptom
Endothelial dysfunction
rhoA GTP-Binding Protein
Protein Kinase Inhibitors
Rho-associated protein kinase
Vasoconstriction
Subjects
Details
- ISSN :
- 20130139
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Drug News & Perspectives
- Accession number :
- edsair.doi.dedup.....53f4251b3a94a1a9fa9aba1920644b1c