Redox Regulation, Oxidative Stress, and Inflammation in Group 3 Pulmonary Hypertension

TY - CHAP

T1 - Redox Regulation, Oxidative Stress, and Inflammation in Group 3 Pulmonary Hypertension

AU - Rudyk, Olena

AU - Aaronson, Philip I.

N1 - Funding Information: Acknowledgments Dr. Olena Rudyk is supported by the British Heart Foundation Intermediate Basic Science Research Fellowship (Sponsor reference FS/14/57/31138) and the British Heart Foundation Centre of Research Excellence Award (King’s College London) (Sponsor reference RE/18/2/34213). Publisher Copyright: © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021

Y1 - 2021

N2 - Group 3 pulmonary hypertension (PH), which occurs secondary to hypoxia lung diseases, is one of the most common causes of PH worldwide and has a high unmet clinical need. A deeper understanding of the integrative pathological and adaptive molecular mechanisms within this group is required to inform the development of novel drug targets and effective treatments. The production of oxidants is increased in PH Group 3, and their pleiotropic roles include contributing to disease progression by promoting prolonged hypoxic pulmonary vasoconstriction and pathological pulmonary vascular remodeling, but also stimulating adaptation to pathological stress that limits the severity of this disease. Inflammation, which is increasingly being viewed as a key pathological feature of Group 3 PH, is subject to complex regulation by redox mechanisms and is exacerbated by, but also augments oxidative stress. In this review, we investigate aspects of this complex crosstalk between inflammation and oxidative stress in Group 3 PH, focusing on the redox-regulated transcription factor NF-κB and its upstream regulators toll-like receptor 4 and high mobility group box protein 1. Ultimately, we propose that the development of specific therapeutic interventions targeting redox-regulated signaling pathways related to inflammation could be explored as novel treatments for Group 3 PH.

AB - Group 3 pulmonary hypertension (PH), which occurs secondary to hypoxia lung diseases, is one of the most common causes of PH worldwide and has a high unmet clinical need. A deeper understanding of the integrative pathological and adaptive molecular mechanisms within this group is required to inform the development of novel drug targets and effective treatments. The production of oxidants is increased in PH Group 3, and their pleiotropic roles include contributing to disease progression by promoting prolonged hypoxic pulmonary vasoconstriction and pathological pulmonary vascular remodeling, but also stimulating adaptation to pathological stress that limits the severity of this disease. Inflammation, which is increasingly being viewed as a key pathological feature of Group 3 PH, is subject to complex regulation by redox mechanisms and is exacerbated by, but also augments oxidative stress. In this review, we investigate aspects of this complex crosstalk between inflammation and oxidative stress in Group 3 PH, focusing on the redox-regulated transcription factor NF-κB and its upstream regulators toll-like receptor 4 and high mobility group box protein 1. Ultimately, we propose that the development of specific therapeutic interventions targeting redox-regulated signaling pathways related to inflammation could be explored as novel treatments for Group 3 PH.

KW - Group 3 Pulmonary Hypertension

KW - Hypoxia

KW - Inflammation

KW - NF-κB

KW - Oxidative stress

KW - Redox signaling

UR - http://www.scopus.com/inward/record.url?scp=85103641621&partnerID=8YFLogxK

U2 - 10.1007/978-3-030-63046-1_13

DO - 10.1007/978-3-030-63046-1_13

M3 - Chapter

C2 - 33788196

AN - SCOPUS:85103641621

T3 - Advances in Experimental Medicine and Biology

SP - 209

EP - 241

BT - Advances in Experimental Medicine and Biology

PB - SPRINGER

ER -