Protective Effect of Right Ventricular Mitochondrial Damage by Cyclosporine A in Monocrotaline-induced Pulmonary Hypertension
Korean Circulation Journal
;
: 1135-1144, 2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-738669
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Permeabilidade
/
Arteríolas
/
Microscopia Eletrônica
/
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina
/
Western Blotting
/
Circulação Pulmonar
/
Reação em Cadeia da Polimerase
/
Monocrotalina
/
Ciclosporina
Tipo de estudo:
Ensaio Clínico Controlado
Idioma:
Inglês
Revista:
Korean Circulation Journal
Ano de publicação:
2018
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS