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World J Methodol. Sep 20, 2025; 15(3): 102688
Published online Sep 20, 2025. doi: 10.5662/wjm.v15.i3.102688
Sotatercept: A novel therapeutic approach for pulmonary arterial hypertension through transforming growth factor-β signaling modulation
Jyoti Bajpai, Mehul Saxena, Akshyaya Pradhan, Surya Kant
Jyoti Bajpai, Surya Kant, Department of Respiratory Medicine, King George’s Medical University, Lucknow 226003, Uttar Pradesh, India
Mehul Saxena, Gandhi Memorial Hospital, King George’s Medical University, Lucknow 226003, Uttar Pradesh, India
Akshyaya Pradhan, Department of Cardiology, King George’s Medical University, Lucknow 226003, Uttar Pradesh, India
Author contributions: Bajpai J and Pradhan A conceptualized the idea and prepared the first draft; Saxena M and Kant S perform the literature search; Kant S and Bajpai J critically reviewed the draft and prose the changes; Bajpai J prepared the final manuscript and submitted; and all authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jyoti Bajpai, MD, Department of Respiratory Medicine, King George’s Medical University, Shahmina Road, Chowk, Lucknow 226003, Uttar Pradesh, India. jyotibajpai33@gmail.com
Received: October 28, 2024
Revised: December 31, 2024
Accepted: January 11, 2025
Published online: September 20, 2025
Processing time: 131 Days and 23.2 Hours
Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease marked by degeneration of the lung’s blood vessels. As the disease progresses, the resistance to blood flow in the pulmonary arteries increases, putting a strain on the right side of the heart as it pumps blood through the lungs. PAH is characterized by changes in the structure of blood vessels and excessive cell growth. Untreated PAH leads to irreversible right-sided heart failure, often despite medical intervention. Patients experience a gradual decline in function until they are unable to perform daily activities. Advances in treatment have improved the prognosis for many PAH patients. Currently approved therapies target the prostacyclin, endothelin, nitric oxide, or phosphodiesterase pathways to slow the progression of the disease. To address the unmet need for effective PAH therapies, research efforts are focused on identifying new targets and developing therapies that specifically address the underlying disease mechanisms and restore vascular wall homeostasis. Among these, sotatercept, a fusion protein that targets the transforming growth factor-β superfamily signaling pathway, has emerged as a promising therapeutic option. In this review, we examine the available evidence from clinical trials to assess the potential of sotatercept as a treatment for PAH.

Keywords: Pulmonary artery; Drugs; Mean pulmonary artery pressure; Transforming growth factor-β pathway; Protein

Core Tip: Sotatercept is an activin receptor type IIA-Fc fusion protein that improve pulmonary artery pressure as well as cardiopulmonary function in pulmonary artery hypertension. It is administered as a subcutaneous injection every three weeks. There are three different pathways involve in pathogenesis of pulmonary arterial hypertension. Recently, a new pathway for pathogenesis of pulmonary arterial hypertension cellular proliferation has been discovered.