Reactive oxygen and nitrogen species in pulmonary hypertension.
Reactive oxygen and nitrogen species in pulmonary hypertension.
复制标题
DOI：
10.1016/j.freeradbiomed.2012.02.041
复制
发表时间：
2012-05-01
影响因子：
7.4
通讯作者：
Gladwin, Mark T.
中科院分区：
文献类型：
--
作者：
Tabima, Diana M.;Frizzell, Sheila;Gladwin, Mark T.
肺血管疾病可以定义为影响肺毛细血管和肺小动脉的疾病，称为肺动脉高压，或影响左心室的疾病，称为肺静脉高压。肺动脉高压（PAH）是一种肺循环疾病，其特征是内皮功能障碍以及内膜和平滑肌增殖。肺血管阻力和压力的逐渐增加会损害右心室的功能，导致心输出量下降、运动能力下降、右心衰竭，最终死亡。虽然这种疾病的原发性和遗传性形式被认为影响美国 5,000 多名患者，但这种疾病也可能继发于先天性心脏病、最晚期的肺部疾病和许多全身性疾病。多项研究表明氧化应激与 PAH 的发生有关。此外，这种氧化应激已被证明与活性氧 (ROS)、活性氮 (RNS) 和一氧化氮 (NO) 信号通路的改变有关，从而生物可利用的 NO 减少，ROS 和 RNS 产量增加。 PAH 中许多经典的 ROS 和 NO 信号通路同时受到破坏，导致烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶和黄嘌呤氧化还原酶表达增加、内皮 NO 合酶 (eNOS) 解偶联、线粒体数量减少以及线粒体功能受损。 ROS/NO 氧化还原稳态的上游失调会损害血管张力，并导致抗凋亡和有丝分裂途径的病理激活，导致细胞增殖和脉管系统的消失。本手稿将回顾有关氧化和亚硝化应激以及内皮功能障碍在肺动脉高压病理生理学中的作用的现有数据，并提供针对该疾病的靶向治疗的描述。
Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies for this disease.
登录
查看更多内容
DOI：
10.1073/pnas.0407224102
发表时间：
2005-01-18
影响因子：
11.1
作者：
Bernatchez, PN;Bauer, PM;Sessa, WC
通讯作者：
Sessa, WC
DOI：
10.1083/jcb.200211104
发表时间：
2003-05-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Biswas G;Anandatheerthavarada HK;Zaidi M;Avadhani NG
通讯作者：
Avadhani NG
影响因子：
64.8
作者：
ARAI, H;HORI, S;NAKANISHI, S
通讯作者：
NAKANISHI, S
影响因子：
20.1
作者：
Brennan, LA;Steinhorn, RH;Black, SM
通讯作者：
Black, SM
影响因子：
4.1
作者：
BOVERIS, A;CHANCE, B
通讯作者：
CHANCE, B