Abstract 17052: Overexpression of Mitofilin in Mouse Heart Increases the ROS Level and Promotes Cardiac Hypertrophy
Background Mitofilin was originally described as heart muscle protein (HMP) because of its abundance in heart tissue, yet its function in the heart has not been investigated.
Methods and Results A significant increase of Mitofilin expression was found in human hypertrophic cardiomyopathy. The transgenic mice over-expressing Mitofilin specifically in cardiomyocytes were generated and cardiac hypertrophy was induced by transverse aortic constriction (TAC) or chronic infusion of isoproterenol (ISO) (Sigma-Aldrich). In mice overexpressing Mitofilin, cardiac hypertrophy was significantly greater than in wild-type (WT) as estimated by HW/BW, echocardiographic measurements as well as cardiac ANP and MYH7 levels after TAC and ISO stimulation. The detailed analysis showed that the hearts from transgenic mice had higher levels of reactive oxygen species (ROS) and lower activities of ROS-detoxifying enzymes (MnSOD and catalase) after hypertrophy induction compared to that of WT mice, and the cRaf-MEK-ERK signal pathway was significantly higher activated in transgenic mouse hearts after TAC and ISO stimulation. Notably, mitochondrial oxidative phosphorylation (OXPHOS) activities in the hearts of transgenic mouse were lower than that of WT mice, with decreased subunit of cytochrome c oxidase and disturbed mitochondria gene expression. These alteration might contribute to the aggravated cardiac hypertrophy in response to TAC and ISO stimulation.
Conclusion Taken together, these data demonstrate that Mitoflin can promote cardiac hypertrophy and reveal what we believe to be a novel role of Mitoflin as a positive regulator for cardiac hypertrophy linking to OXPHOS.
- © 2012 by American Heart Association, Inc.