Document Detail

Targeting RhoA/ROCK pathway in pulmonary arterial hypertension.
MedLine Citation:
PMID:  22449260     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease with a complex pathogenesis. It is often associated with an increased vascular resistance, whilst in the more advanced stages there is a remodelling of the vascular walls. PAH has an intricate involvement of various signaling pathways, including the ras homolog family member A (RhoA)-Rho kinase (ROCK) axis. Currently, available therapies are not always able to significantly slow PAH progression. Therefore, newer approaches are needed.
AREAS COVERED: In this review, areas covered include the role of the RhoA/ROCK in PAH pathogenesis and the plausibility of its therapeutic targeting. Furthermore, various inhibitory compounds are discussed, including Fasudil and SB-772077-B.
EXPERT OPINION: Currently, specific RhoA/ROCK inhibition is the most promising therapeutic approach for PAH. Research has shown that it suppresses both the components of this axis and the upstream upregulating mediators. An inhaled RhoA/ROCK inhibitor may be a successful future therapy; however, further clinical trials are needed to support this approach.
Sabina Antonela Antoniu
Publication Detail:
Type:  Journal Article; Review     Date:  2012-03-27
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  16     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-06     Completed Date:  2012-08-07     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  355-63     Citation Subset:  IM    
'Gr T Popa' University of Medicine and Pharmacy Iaşi, Pulmonary Disease University Hospital, Department of Medicine II -Pulmonary Disease, Romania.
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MeSH Terms
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology,  therapeutic use
Hypertension, Pulmonary / drug therapy*,  metabolism
Phosphodiesterase 5 Inhibitors / pharmacology,  therapeutic use
Protein Kinase Inhibitors / pharmacology,  therapeutic use
Signal Transduction
rho-Associated Kinases / antagonists & inhibitors*,  metabolism
rhoA GTP-Binding Protein / antagonists & inhibitors*,  metabolism
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Phosphodiesterase 5 Inhibitors; 0/Protein Kinase Inhibitors; EC Kinases; EC GTP-Binding Protein

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