RhoA/Rho-kinase signaling: a therapeutic target in pulmonary hypertension.
RhoA/Rho-kinase signaling: a therapeutic target in pulmonary hypertension.
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DOI：
10.2147/vhrm.s4711
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发表时间：
2009
影响因子：
2.9
通讯作者：
White RE
中科院分区：
文献类型：
--
作者：
Barman SA;Zhu S;White RE
肺动脉高压（PAH）是一种毁灭性疾病，其特征是由于肺血管收缩和血管重塑以及炎症导致的肺动脉压和血管阻力进行性升高。Rho激酶（ROCKs）是小G蛋白RhoA的最佳效应子之一，并且ROCKs通过抑制肌球蛋白轻链磷酸酶和激活下游介质而参与多种细胞功能，包括肌细胞收缩、增殖和血管炎症。动物模型中的大量证据表明，RhoA/ROCK信号传导增强通过引起肺血管的收缩和重塑而在肺动脉高压的发病机制中发挥重要作用。动物和临床研究均表明，ROCK抑制剂可有效治疗重度PAH，且风险极小，这支持了ROCK是肺动脉高压重要治疗靶点的前提，并且ROCK抑制剂是治疗这种毁灭性疾病的一类有前途的新药。
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.