March 3, 2026Open Access

Sotatercept Reverses SIN3a Deficiency-Driven PAH by Reprogramming BMPR2/TGF-β-HIF-1α Signaling Pathways

Key Points

Sotatercept significantly restores SIN3a expression, effectively reversing pulmonary arterial hypertension severity.
The study observes improved BMPR2 and TGF-β signaling alongside reduced pulmonary vascular remodeling and dysfunction.

Structured PICO

Does Sotatercept attenuate pulmonary vascular remodeling and right ventricular dysfunction in preclinical models of PAH?

Population

Preclinical models of pulmonary arterial hypertension (PAH) involving pulmonary artery smooth muscle cells (PASMC) and SIN3a deficiency

Intervention

Sotatercept

Outcome

SIN3a expression, BMPR2 and TGF-β signaling, pulmonary vascular remodeling, and right ventricular dysfunctionsurrogate

Sotatercept acts as a disease-modifying therapy in PAH by restoring SIN3a expression and rebalancing BMPR2/TGF-β signaling to attenuate vascular remodeling and right ventricular dysfunction.

Abstract

SIN3a is a central epigenetic regulator of PASMC homeostasis that integrates oxidative stress, inflammation, and fibrotic signaling. Loss of SIN3a accelerates PAH progression, whereas Sotatercept restores SIN3a expression, rebalances BMPR2 and TGF-β signaling, and attenuates pulmonary vascular remodeling and right ventricular dysfunction. Together, these findings identify SIN3a as a disease-relevant therapeutic target and support the use of Sotatercept as a disease-modifying approach for pulmonary vascular disease.

Sotatercept Reverses SIN3a Deficiency-Driven PAH by Reprogramming BMPR2/TGF-β-HIF-1α Signaling Pathways

Key Points

Structured PICO

Abstract

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