Sotatercept Reverses SIN3a Deficiency-Driven PAH by Reprogramming BMPR2/TGF-β-HIF-1α Signaling Pathways
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.
Authors
- María Teresa Ochoa (ORCID: https://orcid.org/0000-0001-6550-5008)
- Anurupa Ghosh (ORCID: https://orcid.org/0000-0001-7028-9792)
- Irene C. Turnbull (ORCID: https://orcid.org/0000-0001-9105-8926)
- Katherine Jankowski (ORCID: https://orcid.org/0009-0003-7205-1341)
- Gregory David (ORCID: https://orcid.org/0000-0002-3371-4558)
- Malik Bisserier
- Shihong Zhang
- Lahouaria Hadri
Institutions
- New York Medical College (US)
- New York University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-02-03
- DOI
- https://doi.org/10.64898/2026.02.03.703590
- Primary Topic
- Pulmonary Hypertension Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00