MPS 11-03 Mitochondrial dysfunction - role in hypertrophic cardiomyocyte

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Abstract

Objective:

Heart disease associated with cardiac hypertrophy is one of the leading health issues worldwide and pathological cardiac hypertrophy is associated with impaired mitochondria leading to myocyte dysfunction. The current study was undertaken to dissect out mitochondrial signaling mechanism in hypertrophic cardiomyocytes.

Design and Method:

To induce cardiac hypertrophy in vitro, h9c2 (2-1) cardiomyocytes were treated with phenylephrine (PE) for 24 h in the absence or presence of PPAR alpha agonist, fenofibrate. Cellular hypertrophy, expression of the fatty acid β-oxidation and mitochondrial genes, mitochondrial trans-membrane potential (Δψm), dynamicity, activity, mitobiogenesis, production of cellular and mitochondrial calcium level and reactive oxygen species (ROS), mitochondrial activity, biogenesis, cell death were examined.

Results:

Cardiac hypertrophy and remodeling of the mitochondria were prevented by PPAR alpha agonist, fenofibrate which also corrected deranged fatty acid oxidation genes in hypertrophic cardiomyocytes. Decrease in mitochondrial trans-membrane potential and dynamicity in PE-treated cardiomyocytes were also blocked by fenofibrate. Significant increase in reactive oxygen species (ROS) and calcium level in hypertrophic condition both at cellular and mitochondrial level was ameliorated by fenofibrate. Furthermore, PE induced impairment of mitochondrial activity and ATP generation were partially checked when cells were co-treated with fenofibrate. Expression of some miRNAs which were found to be putative regulators of mitochondrial marker gene, voltage dependent anion channel (VDAC), were altered in hypertrophic cardiomyocytes which were restored when the cells were co-treated with fenofibrate.

Conclusions:

Overall, the results demonstrate that PPAR alpha signaling is critically involved in mitochondrial dysfunction in hypertrophic cardiomyocytes in which miRNAs might play a significant role.

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