Group 3 Pulmonary Hypertension: From Bench to Bedside

Abstract

Pulmonary hypertension (PH) because of chronic lung disease is categorized as Group 3 PH in the most recent classification system. Prevalence of these diseases is increasing over time, creating a growing need for effective therapeutic options. Recent approval of the first pulmonary arterial hypertension therapy for the treatment of Group 3 PH related to interstitial lung disease represents an encouraging advancement. This review focuses on molecular mechanisms contributing to pulmonary vasculopathy in chronic hypoxia, the pathology and epidemiology of Group 3 PH, the right ventricular dysfunction observed in this population and clinical trial data that inform the use of pulmonary vasodilators in Group 3 PH.

Oral Pulmonary Arterial Hypertension-Targeted Therapy in Patients with Pulmonary Hypertension due to Interstitial Lung Disease

“…The use of PAH-targeted therapy may be associated with improved hemodynamics and a reduction in NT-proBNP levels in a subset of patients with PH-ILD, and the results of this study raise clinical equipoise for further study. The future application of precision medicine to aid in phenotyping patients with WSPH Group 3 PH may help clinicians better understand which patients are likely to bene t from PAH-targeted therapy [32]. Additionally, given what is known about the bene cial effects of inhaled Treprostinil in patients with PH-ILD, studies evaluating the route of administration of PAH-targeted therapy is also warranted.…”

The Evolving Management and Treatment Options for Patients with Pulmonary Hypertension: Current Evidence and Challenges

“…While this is true, chronic hypoxia has also been linked to the activity of several mediators affecting vascular structure and function similar to the vascular remodeling noted in PAH. 91 , 92 Supplemental oxygen may be helpful in reversing hypoxic vasoconstriction in early stages, but as disease progresses and hypoxia becomes a more chronic fixture, vascular remodeling becomes a more significant cause of rising pulmonary vascular resistance. As with PAH, endothelial biology plays a key role in the pulmonary vascular response to hypoxia and is influenced by TGF-B1 and hypoxia-inducible factor 1-alpha (HIF-1a) signaling pathways.…”

“…As with PAH, endothelial biology plays a key role in the pulmonary vascular response to hypoxia and is influenced by TGF-B1 and hypoxia-inducible factor 1-alpha (HIF-1a) signaling pathways. 81 , 91 , 93 , 94 In experimental models, chronic hypoxia induces expression of vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2 via HIF-1a. 91 , 95 , 96 Hypoxia also induces expression of TGF-B1 and thereby enhances production of PDGF-B.…”

“… 81 , 91 , 93 , 94 In experimental models, chronic hypoxia induces expression of vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2 via HIF-1a. 91 , 95 , 96 Hypoxia also induces expression of TGF-B1 and thereby enhances production of PDGF-B. PDGF-B has been shown to promote VEGFA expression and hence hypoxia-induced endothelial proliferation.…”

“…PDGF-B has been shown to promote VEGFA expression and hence hypoxia-induced endothelial proliferation. 91 , 97 Chronic hypoxia is a stimulus for serotonin release, which in turn stimulates vasoconstriction and promotes endothelial proliferation and smooth muscle hypertrophy. 92 , 98 Hypoxia is reported to decrease endothelial cell nitric oxide production and increase endothelin release.…”