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Updated: May 23, 2025

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets
Published on: May 11, 2015
Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape
Christopher V Flores1, Stephen Y Chan1
1Center for Pulmonary Vascular Biology and Medicine, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Background:
Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disease driven by vascular remodeling, right ventricular (RV) dysfunction, and metabolic and inflammatory dysregulation. Current therapies primarily target vasodilation to relieve symptoms but do not reverse disease progression. The recent approval of sotatercept, which modulates BMP/TGF-β signaling, marks a shift toward anti-remodeling therapies. Building on this, recent preclinical advances have identified promising therapeutic targets and potentially disease-modifying treatments.
Areas Covered:
This review synthesizes the evolving preclinical landscape of emerging PAH therapeutic targets and drugs, highlighting innovative approaches aimed at addressing the underlying mechanisms of disease progression. Additionally, we discuss novel therapeutic strategies under development.
Expert Opinion:
Recent advances in PAH research have identified novel therapeutic targets beyond vasodilators, including modulation of BMP/TGF-β signaling, metabolic programs, epigenetics, cancer-related signaling, the extracellular matrix, and immune pathways, among others. Sotatercept represents a significant advance in therapies that go beyond vasodilation, and long-term safety, efficacy, and durability are being assessed. Future treatment strategies will focus on precision approaches, noninvasive technologies, and regenerative biology to improve outcomes and reverse vascular remodeling.
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