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Targeting RhoA/ROCK pathway in pulmonary arterial hypertension

  作者 Antoniu, SA  
  选自 期刊  Expert Opinion on Therapeutic Targets;  卷期  2012年16-4;  页码  355-363  
  关联知识点  
 

[摘要]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.

 
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