Mechanical signaling through cell-matrix interactions plays a major role in progressive vascular remodeling in pulmonary arterial hypertension (PAH). Matrix metalloproteinase-8 (MMP-8) is an interstitial collagenase involved in regulating inflammation and fibrosis of the lung and systemic vasculature, but its role in PAH pathogenesis remains unexplored. To evaluate MMP-8 as a modulator of pathogenic mechanical signaling in PAH. MMP-8 levels were measured in plasma from pulmonary hypertension (PH) patients and controls by ELISA. MMP-8 vascular expression was examined in lung tissue from PAH patients and rodent models of PH. MMP-8–/– and MMP-8+/+ mice were exposed to normobaric hypoxia or normoxia for 4-8 weeks. PH severity was evaluated by right ventricular systolic pressure (RVSP), echocardiography, pulmonary artery (PA) morphometry and immunostaining. Proliferation, migration, matrix component expression, and mechanical signaling were assessed in MMP-8–/– and MMP-8+/+ pulmonary artery smooth muscle cells (PASMCs).
