» Articles » PMID: 29047079

Molecular Basis of Nitrative Stress in the Pathogenesis of Pulmonary Hypertension

Overview
Date 2017 Oct 20
PMID 29047079
Citations 4
Authors
Affiliations
Soon will be listed here.
Abstract

Pulmonary hypertension (PH) is a lung vascular disease with marked increases in pulmonary vascular resistance and pulmonary artery pressure (>25 mmHg at rest). In PH patients, increases in pulmonary vascular resistance lead to impaired cardiac output and reduced exercise tolerance. If untreated, PH progresses to right heart failure and premature lethality. The mechanisms that control the pathogenesis of PH are incompletely understood, but evidence from human and animal studies implicate nitrative stress in the development of PH. Increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) result in nitrative stress, which in turn induces posttranslational modification of key proteins important for maintaining pulmonary vascular homeostasis. This affects their functions and thereby contributes to the pathogenesis of PH. In this chapter, molecular mechanisms underlying nitrative stress-induced PH are reviewed, molecular sources of ROS and RNS are delineated, and evidence of nitrative stress in PH patients is described. A better understanding of such mechanisms could lead to the development of novel treatments for PH.

Citing Articles

RNA m6A methylation and regulatory proteins in pulmonary arterial hypertension.

Wang Z, Zhang Y, Shi J, Yan Y, Zhao L, Kou J Hypertens Res. 2024; 47(5):1273-1287.

PMID: 38438725 DOI: 10.1038/s41440-024-01607-9.


Endothelial PHD2 deficiency induces nitrative stress suppression of caveolin-1 in pulmonary hypertension.

Liu B, Peng Y, Yi D, Machireddy N, Dong D, Ramirez K Eur Respir J. 2022; 60(6).

PMID: 35798360 PMC: 9791795. DOI: 10.1183/13993003.02643-2021.


Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells.

Wang S, Chang M, Shiau J, Farooqi A, Huang Y, Tang J Molecules. 2022; 27(5).

PMID: 35268676 PMC: 8911617. DOI: 10.3390/molecules27051576.


Endothelial cells in the pathogenesis of pulmonary arterial hypertension.

Evans C, Cober N, Dai Z, Stewart D, Zhao Y Eur Respir J. 2021; 58(3).

PMID: 33509961 PMC: 8316496. DOI: 10.1183/13993003.03957-2020.

References
1.
Wever R, Van Dam T, van Rijn H, de Groot F, Rabelink T . Tetrahydrobiopterin regulates superoxide and nitric oxide generation by recombinant endothelial nitric oxide synthase. Biochem Biophys Res Commun. 1997; 237(2):340-4. DOI: 10.1006/bbrc.1997.7069. View

2.
Cracowski J, Cracowski C, Bessard G, Pepin J, Bessard J, Schwebel C . Increased lipid peroxidation in patients with pulmonary hypertension. Am J Respir Crit Care Med. 2001; 164(6):1038-42. DOI: 10.1164/ajrccm.164.6.2104033. View

3.
Yokoyama M, Hirata K . Endothelial nitric oxide synthase uncoupling: Is it a physiological mechanism of endothelium-dependent relaxation in cerebral artery?. Cardiovasc Res. 2006; 73(1):8-9. DOI: 10.1016/j.cardiores.2006.11.009. View

4.
Bowers R, Cool C, Murphy R, Tuder R, Hopken M, Flores S . Oxidative stress in severe pulmonary hypertension. Am J Respir Crit Care Med. 2004; 169(6):764-9. DOI: 10.1164/rccm.200301-147OC. View

5.
Zhao Y, Liu Y, Stan R, Fan L, Gu Y, Dalton N . Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci U S A. 2002; 99(17):11375-80. PMC: 123264. DOI: 10.1073/pnas.172360799. View