A novel insight into the mechanism of pulmonary hypertension involving caveolin-1 deficiency and endothelial nitric oxide synthase activation.
A novel insight into the mechanism of pulmonary hypertension involving caveolin-1 deficiency and endothelial nitric oxide synthase activation.
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DOI：
10.1016/j.tcm.2010.02.003
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发表时间：
2009-10
影响因子：
9.3
通讯作者：
Malik, Asrar B.
中科院分区：
文献类型：
--
作者：
Zhao, You-Yang;Malik, Asrar B.
重度肺动脉高压(PH)的特征是肺血管阻力进行性增加和血管重构，导致右心衰竭和早期死亡。我们最近的研究采用了带有小窝蛋白-1(Cav1)和eNOS(NOS3)基因缺失的新型小鼠模型，研究表明，Cav1−/−肺中eNOS的持续激活导致蛋白激酶G(PKG)的酪氨酸硝化和活性降低，从而导致PH。本文综述了特发性肺动脉高压患者肺组织中eNOS活化和PKG硝化伴随Cav1缺乏症的发现。提示靶向PKG硝化对PH的治疗具有潜在的应用价值。在这里，我们将对Cav1调节的eNOS活性及其在PH发病机制中的基础作用的现有知识进行综述。
Severe pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary vascular resistance and vascular remodeling leading to right heart failure and early death. Our recent studies employing the novel mouse model with genetic deletions of caveolin-1 (Cav1) and eNOS (NOS3) have demonstrated that persistent eNOS activation in Cav1−/− lungs results in tyrosine nitration of protein kinase G (PKG) and impairment of its activity, which thereby induces PH. The finding of eNOS activation and PKG nitration concomitant with Cav1 deficiency was recapitulated in lungs from patients with idiopathic pulmonary arterial hypertension. These data suggest targeting PKG nitration has potential value for the treatment of PH. Here, we will review the current knowledge about Cav1-regulated eNOS activity and its fundamental role in the pathogenesis of PH.
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