American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Nov 2016
A Selective TGFβ Ligand Trap Attenuates Pulmonary Hypertension.
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. ⋯ Our findings are consistent with a pathogenetic role of TGF-β1/3, demonstrating the efficacy and tolerability of selective TGF-β ligand blockade for improving hemodynamics, remodeling, and survival in multiple experimental PH models.