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

Abstract

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.

Keywords: Group 3 Pulmonary Hypertension; Hypoxia; Inflammation; NF-κB; Oxidative stress; Redox signaling.