Molecular basis of nitrative stress in the pathogenesis of pulmonary hypertension

Colin E. Evans, You Yang Zhao*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages33-45
Number of pages13
DOIs
StatePublished - 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume967
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Funding

British Heart Foundation Center of Research Excellence, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Keywords

  • Cyclic guanosine monophosphate
  • Nitric oxide synthases
  • Phosphodiesterase type 5
  • Protein kinase G
  • Pulmonary hypertension
  • Reactive nitrogen species
  • Reactive oxygen species
  • Soluble guanylate cyclase

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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