P ulmonary arterial hypertension (PAH) is a progressive disease characterized by a marked increase in pulmonary arterial pressure and right ventricular hypertrophy (RV/LV+Sep). 1 The increase in pulmonary vascular resistance is due to adventitial, medial, and intimal thickening of small pulmonary arteries, resulting from fibroblast, smooth muscle, and endothelial cell proliferation.2 Increased proliferation of pulmonary arterial smooth muscle cells (PASMCs) and resistance to apoptosis is a central feature of diverse forms of PAH.2,3 Without treatment, progression of pulmonary hypertension leads to right ventricular (RV) failure and death.Recent studies have highlighted a key role for the transforming growth factor-β/bone morphogenetic protein type II receptor (BMPR-II) superfamily in the pathobiology of PAH.4,5 Some 6% to 10% of cases of severe PAH have a further affected family member. Mutations in the BMPR-II are now known to underlie at least 70% of cases of heritable PAH 6,7 and are found in 10% to 40% of cases of apparently sporadic PAH. Objective: We reasoned that chloroquine, based on its ability to inhibit autophagy and block lysosomal degradation of the bone morphogenetic protein type II receptor (BMPR-II), might exert beneficial effects in this disease.
Methods and Results: PAH was induced in male Sprague