{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:14:15Z","timestamp":1781828055322,"version":"3.54.5"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014Next-Generation EU through the Italian Ministry of University and Research","award":["M4C2-I1.3"],"award-info":[{"award-number":["M4C2-I1.3"]}]},{"name":"European Union\u2014Next-Generation EU through the Italian Ministry of University and Research","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}]},{"name":"European Union\u2014Next-Generation EU through the Italian Ministry of University and Research","award":["CUP I53C22001440006"],"award-info":[{"award-number":["CUP I53C22001440006"]}]},{"name":"European Union\u2014Next-Generation EU through the Italian Ministry of University and Research","award":["PRIN-PNRR 2022S74XWB"],"award-info":[{"award-number":["PRIN-PNRR 2022S74XWB"]}]},{"name":"European Union\u2014Next-Generation EU through the Italian Ministry of University and Research","award":["CUP I53D23005240006"],"award-info":[{"award-number":["CUP I53D23005240006"]}]},{"name":"European Union\u2014Next-Generation EU through the Italian Ministry of University and Research","award":["PNRR-MR1-2022-12376879"],"award-info":[{"award-number":["PNRR-MR1-2022-12376879"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sotatercept selectively binds free activins and growth differentiation factors by reproducing the binding domain of the activin receptor type IIA (ACTRIIA). The sequester of activins blunts the downstream signaling pathway, resulting in the reactivation of the bone morphogenic protein (BMP) receptor type 2 signaling and inhibition of pathological remodeling in pulmonary circulation. The balance between proliferative and antiproliferative pathways is restored, with a favorable impact on the progression of pulmonary arterial hypertension (PAH). Sotatercept, first approved for the treatment of hematological disorders such as anemia, has recently received approval as a drug in the treatment of group 1 PAH, either in United States or Europe. In this review, we will discuss the application of sotatercept and its cross reactivity in function alone or in combination with other drugs currently used for PAH. We will try also to further discuss what is known regarding the hematological effects of sotatercept, both from preclinical and clinical studies points of view, since they are the root of the side effects seen in PAH trials, such as bleeding and increased hemoglobin.<\/jats:p>","DOI":"10.3390\/ijms26104851","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T07:34:03Z","timestamp":1747640043000},"page":"4851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sotatercept: A Crosstalk Between Pathways and Activities in the Pulmonary Circulation and Blood"],"prefix":"10.3390","volume":"26","author":[{"given":"Rosalinda","family":"Madonna","sequence":"first","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Area, Cardiology Division, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-5621","authenticated-orcid":false,"given":"Sandra","family":"Ghelardoni","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology and Critical Area, Laboratory of Biochemistry, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2200879","DOI":"10.1183\/13993003.00879-2022","article-title":"2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"61","author":"Humbert","year":"2023","journal-title":"Eur. 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