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Pulmonary arterial hypertension is a progressive disease of the small pulmonary vasculature leading to right heart failure. Recent studies revealed that mitochondria are key roles in the pathophysiology of heart failure. But little is known about mitochondrial dysfunction in pulmonary arterial hypertension. We hypothesized that mitochondrial permeability transition pore blocker, cyclosporine A, prevent right heart failure in monocrotaline (MCT) induced pulmonary arterial hypertension.
Twenty four 8-week-old rats were randomized to control, MCT (60 mg/kg, sc) and MCT plus cyclosporine A (10 mg/kg/day, po) treatment groups. Four weeks later, right ventricular hypertrophy (right ventricle/left ventricle+septum ratio, RV/LV+S) and ultrastructural changes of right ventricle were done. Western blot for cyclophilin D, Tom20, Tim23, Drp1 and Mfn2 were performed.
RV/LV+S ratio was significantly increased in MCT group compared with that of the controls (0.50±0.06 vs. 0.29±0.02), but right ventricular hypertrophy was more than MCT group in cyclosporine A treatment group (0.57±0.01). In transmission electron microscopy, right ventricular mitochondria were swelled, disrupted, and disorganized in MCT group, but cyclosporine A treatment prevent mitochondrial damage.
Mitochondrial permeability transition pore blocker, cyclosporine A, reduce MCT induced right ventricular mitochondrial damage. Mitochondrial permeability transition pore blocker may provide an additional strategy for the treatment of pulmonary arterial hypertension.
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Pulmonary Hypertension: Pre-Clinical, Clinical, Biomarkers
Abstract Category: 27. Pulmonary Hypertension
Presentation Number: 1294-150
- 2013 American College of Cardiology Foundation