Reactive oxygen species in pulmonary vascular remodeling

Saurabh Aggarwal, Christine M. Gross, Shruti Sharma, Jeffrey R. Fineman, Stephen M. Black

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress, and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the antioxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphateoxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting cofactor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)1011-1034
Number of pages24
JournalComprehensive Physiology
Volume3
Issue number3
DOIs
StatePublished - Dec 1 2013

Fingerprint

Reactive Oxygen Species
Lung
Pulmonary Hypertension
Nitric Oxide Synthase Type III
Pulmonary Artery
Antioxidants
Peroxisomes
Xanthine Oxidase
Arterioles
Vascular Smooth Muscle
Organelles
NAD
Hypertrophy
Smooth Muscle Myocytes
Hyperplasia
Blood Vessels
Arginine
Vascular Remodeling
Mitochondria
Cytoplasm

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Physiology (medical)

Cite this

Aggarwal, S., Gross, C. M., Sharma, S., Fineman, J. R., & Black, S. M. (2013). Reactive oxygen species in pulmonary vascular remodeling. Comprehensive Physiology, 3(3), 1011-1034. https://doi.org/10.1002/cphy.c120024

Reactive oxygen species in pulmonary vascular remodeling. / Aggarwal, Saurabh; Gross, Christine M.; Sharma, Shruti; Fineman, Jeffrey R.; Black, Stephen M.

In: Comprehensive Physiology, Vol. 3, No. 3, 01.12.2013, p. 1011-1034.

Research output: Contribution to journalArticle

Aggarwal, S, Gross, CM, Sharma, S, Fineman, JR & Black, SM 2013, 'Reactive oxygen species in pulmonary vascular remodeling', Comprehensive Physiology, vol. 3, no. 3, pp. 1011-1034. https://doi.org/10.1002/cphy.c120024
Aggarwal, Saurabh ; Gross, Christine M. ; Sharma, Shruti ; Fineman, Jeffrey R. ; Black, Stephen M. / Reactive oxygen species in pulmonary vascular remodeling. In: Comprehensive Physiology. 2013 ; Vol. 3, No. 3. pp. 1011-1034.
@article{6bbb579735bd4e7d824f2f3bc62b9a63,
title = "Reactive oxygen species in pulmonary vascular remodeling",
abstract = "The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress, and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the antioxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphateoxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting cofactor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension.",
author = "Saurabh Aggarwal and Gross, {Christine M.} and Shruti Sharma and Fineman, {Jeffrey R.} and Black, {Stephen M.}",
year = "2013",
month = "12",
day = "1",
doi = "10.1002/cphy.c120024",
language = "English (US)",
volume = "3",
pages = "1011--1034",
journal = "Comprehensive Physiology",
issn = "2040-4603",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Reactive oxygen species in pulmonary vascular remodeling

AU - Aggarwal, Saurabh

AU - Gross, Christine M.

AU - Sharma, Shruti

AU - Fineman, Jeffrey R.

AU - Black, Stephen M.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress, and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the antioxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphateoxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting cofactor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension.

AB - The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress, and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the antioxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphateoxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting cofactor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension.

UR - http://www.scopus.com/inward/record.url?scp=84891671846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891671846&partnerID=8YFLogxK

U2 - 10.1002/cphy.c120024

DO - 10.1002/cphy.c120024

M3 - Article

VL - 3

SP - 1011

EP - 1034

JO - Comprehensive Physiology

JF - Comprehensive Physiology

SN - 2040-4603

IS - 3

ER -