A Selective Transforming Growth Factor-β Ligand Trap Attenuates Pulmonary Hypertension

Rationale: Transforming growth factor-β (TGF-β) ligands signal via type I and type II serine-threonine kinase receptors to regulate broad transcriptional programs. Excessive TGF-β–mediated signaling is implicated in the pathogenesis of pulmonary arterial hypertension, based in part on the ability of broad inhibition of activin-like kinase (ALK) receptors 4/5/7 recognizing TGF-β, activin, growth and differentiation factor, and nodal ligands to attenuate experimental pulmonary hypertension (PH). These broad inhibition strategies do not delineate the specific contribution of TGF-β versus a multitude of other ligands, and their translation is limited by cardiovascular and systemic toxicity.Objectives: We tested the impact of a soluble TGF-β type II receptor extracellular domain expressed as an immunoglobulin–Fc fusion protein (TGFBRII-Fc), serving as a selective TGF-β1/3 ligand trap, in several experimental PH models.Methods: Signaling studies used cultured human pulmonary artery smooth muscle cells. PH was s...