Nitric Oxide Deficiency and Endothelial Dysfunction in Pulmonary Arterial Hypertension
Nitric Oxide Deficiency and Endothelial Dysfunction in Pulmonary Arterial Hypertension
复制标题
DOI：
10.1164/rccm.201304-0686pp
复制
发表时间：
2013-09-15
影响因子：
24.7
通讯作者：
Gladwin, Mark T.
中科院分区：
文献类型：
--
作者：
Klinger, James R.;Abman, Steven H.;Gladwin, Mark T.
一氧化氮（NO）信号在调节肺循环血管张力和重塑中起重要作用，但其在肺血管疾病发病机制中的作用尚不完全清楚。在肺血管疾病动物模型和肺动脉高压患者中发现了许多NO合成和信号传导异常。许多这些异常已经成为治疗肺动脉高压的新疗法的目标。然而，目前尚不清楚NO信号的改变在多大程度上促进了肺动脉高压反应，或者仅仅反映了潜在疾病引起的异常。这一观点探讨了目前对肺动脉高压疾病中NO信号改变的理解，并讨论了这些改变如何有助于肺动脉高压的发病机制。本文回顾了目前针对NO信号通路的肺动脉高压治疗方法的有效性和局限性，以及利用该途径逆转肺动脉高压改变的研究治疗方法的最新进展。
Nitric oxide (NO) signaling plays a major role in modulating vascular tone and remodeling in the pulmonary circulation, but its role in the pathogenesis of pulmonary vascular diseases is still not completely understood. Numerous abnormalities of NO synthesis and signaling have been identified in animal models of pulmonary vascular disease and in humans with pulmonary hypertension. Many of these abnormalities have become targets of new therapies for the treatment of pulmonary hypertension. However, it is unclear to what extent alterations in NO signaling contribute to pulmonary hypertensive responses or merely reflect abnormalities induced by the underlying disease. This perspective examines the current understanding of altered NO signaling in pulmonary hypertensive diseases and discusses how these alterations may contribute to the pathogenesis of pulmonary hypertension. The efficacy and limitations of presently available therapies for pulmonary hypertension that target NO signaling are reviewed along with an update on investigational therapies that use this pathway to reverse pulmonary hypertensive changes.