Abstract 19307: A Selective Tgfβ Ligand Trap Attenuates Pulmonary Hypertension

Introduction: Transforming Growth Factor-β (TGFβ) ligands signal via type I and type II serine-threonine kinase receptors to regulate broad transcriptional programs. Excessive TGFβ-mediated signaling is implicated in the pathogenesis of pulmonary arterial hypertension (PAH), based in part on the ability of broad inhibitors of TGFβ/Activin/GDF/Nodal receptors ALK4/5/7 to attenuate experimental pulmonary hypertension (PH). These broad inhibition strategies do not delineate the specific contribution of TGFβ vs. a multitude of other ligands, and their translation is limited by cardiovascular and systemic toxicity. Hypothesis: We tested whether or not TGFBRII-Fc, a selective TGFβ1/3 ligand trap, reverses PH and vascular remodeling in experimental PH models. Methods: Signaling studies utilized cultured human pulmonary artery smooth muscle cells. PH was studied in monocrotaline-treated Sprague-Dawley rats, SUGEN/hypoxia-treated Sprague-Dawley rats and SUGEN/hypoxia-treated C57BL/6 mice. PH, cardiac function, vas...