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Mitochondrial mechanism of right ventricular failure (RVF)
Author(s) -
Qipshidze Natia,
Tyagi Neetu,
Metreveli Naira,
Tyagi Suresh C
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1127.3
Subject(s) - mitophagy , oxidative stress , pressure overload , mitochondrion , medicine , fibrosis , cardiology , constriction , muscle hypertrophy , endocrinology , cardiac function curve , heart failure , pharmacology , chemistry , autophagy , cardiac hypertrophy , biochemistry , apoptosis
Sustained pressure overload induces pathological cardiac dysfunction, linked to mitochondrial dysfunction (mitophagy) during RVF. We tested whether mitophagy division inhibitor (Mdivi‐I) mitigates oxidative stress and leads to reverse pre‐established advanced hypertrophy, fibrosis, and RV dysfunction. To verify this, C57 (less), FVB (intermediate), and C3H (most resistant to oxidative stress) strains of mice underwent pulmonary artery constriction (PAC) for 4 weeks with or without the Mdivi‐I (50 mg/kg/day) treatment. After PAC mice developed increased cardiac mass, lowered ejection fraction, triggering oxidative stress, and mitochondrial dysfunction. Mdivi‐I treatment reversed hypertrophy and fibrosis, lowered oxidative stress, and improved chamber and myocyte function, whereas untreated hearts worsened, To further support the claim of mitophagy occurrence during RVF, the levels of LC3A/B and P62 were measured. LC3A/B was increased in RV of PAC mice. Similarly, increased P62 protein level was also observed in RV of PAC mice. Treatment with Mdivi‐I abolished this affect in PAC mice. RV pressure in PAC mice was increase up to 55±3 mmHg, treatment with Mdivi‐I decreased the pressure to 32±4 mmHg. These results suggest that, Mdivi‐I treatment reduces oxidative stress and ameliorates mitochondrial dysfunction that results in protection of RVF against mytophagy during PAH.