Protective Effect of Right Ventricular Mitochondrial Damage by Cyclosporine A in Monocrotaline-induced Pulmonary Hypertension
- Author:
Dong Seok LEE
1
;
Yong Wook JUNG
Author Information
- Publication Type:Original Article
- Keywords: Pulmonary circulation; Pulmonary hypertension; Heart ventricles; Mitochondria
- MeSH: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adenine Nucleotide Translocator 1; Arterioles; Blotting, Western; Caspase 3; Cell Death; Cyclophilins; Cyclosporine; Heart Failure; Heart Ventricles; Hypertension; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Microscopy, Electron; Mitochondria; Monocrotaline; Pathology; Permeability; Polymerase Chain Reaction; Pulmonary Circulation; Rats, Sprague-Dawley; Reverse Transcription
- From:Korean Circulation Journal 2018;48(12):1135-1144
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND OBJECTIVES: Mitochondria play a key role in the pathophysiology of heart failure and mitochondrial permeability transition pore (MPTP) play a critical role in cell death and a critical target for cardioprotection. The aim of this study was to evaluate the protective effects of cyclosporine A (CsA), one of MPTP blockers, and morphological changes of mitochondria and MPTP related proteins in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). METHODS: Eight weeks old Sprague-Dawley rats were randomized to control, MCT (60 mg/kg) and MCT plus CsA (10 mg/kg/day) treatment groups. Four weeks later, right ventricular hypertrophy (RVH) and morphological changes of right ventricle (RV) were done. Western blot and reverse transcription polymerase chain reaction (RT-PCR) for MPTP related protein were performed. RESULTS: In electron microscopy, CsA treatment prevented MCT-induced mitochondrial disruption of RV. RVH was significantly increased in MCT group compared to that of the controls but RVH was more increased with CsA treatment. Thickened medial wall thickness of pulmonary arteriole in PAH was not changed after CsA treatment. In western blot, caspase-3 was significantly increased in MCT group, and was attenuated in CsA treatment. There were no significant differences in voltage-dependent anion channel, adenine nucleotide translocator 1 and cyclophilin D expression in western blot and RT-PCR between the 3 groups. CONCLUSIONS: CsA reduces MCT induced RV mitochondrial damage. Although, MPTP blocking does not reverse pulmonary pathology, it may reduce RV dysfunction in PAH. The results suggest that it could serve as an adjunctive therapy to PAH treatment.
