Madonna Rosalinda, Ghelardoni Sandra
Department of Surgical, Medical and Molecular Pathology and Critical Area, Cardiology Division, University of Pisa, 56124 Pisa, Italy.
Department of Surgical, Medical and Molecular Pathology and Critical Area, Laboratory of Biochemistry, University of Pisa, 56124 Pisa, Italy.
Int J Mol Sci. 2025 May 19;26(10):4851. doi: 10.3390/ijms26104851.
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.
索他西普通过重现IIA型激活素受体（ACTRIIA）的结合域，选择性地结合游离的激活素和生长分化因子。激活素的螯合减弱了下游信号通路，导致2型骨形态发生蛋白（BMP）受体信号的重新激活，并抑制肺循环中的病理重塑。增殖和抗增殖途径之间的平衡得以恢复，对肺动脉高压（PAH）的进展产生有利影响。索他西普最初被批准用于治疗贫血等血液系统疾病，最近在美国或欧洲均已获批作为治疗1类PAH的药物。在这篇综述中，我们将讨论索他西普的应用及其单独或与目前用于PAH的其他药物联合使用时的交叉反应。我们还将从临床前和临床研究的角度，进一步讨论索他西普血液学效应的相关情况，因为这些效应是PAH试验中出现的副作用（如出血和血红蛋白升高）的根源。
