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RAPID ONSET OXIDATIVE MYOCARDIAL INSULT AND LOSS OF CARDIAC FUNCTION

Please use this identifier to cite or link to this item: http://hdl.handle.net/1811/51778

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Title: RAPID ONSET OXIDATIVE MYOCARDIAL INSULT AND LOSS OF CARDIAC FUNCTION
Creators: Banerjee, Jaideep
Advisor: Sen, Chandan
Issue Date: 2012-02
Abstract: Background- Dicer endonuclease, critical for maturation of microRNAs (miRNAs), is depleted in heart failure patients with certain forms of cardiomyopathy. We sought to elucidate the mechanisms underlying the rapid loss of cardiac function following cardiac-specific Dicer deletion in adult mice. Methods and Results- Conditional Dicer deletion was achieved by a tamoxifen-inducible Cre recombinase in the adult murine myocardium. Heart function, determined using MRI and echocardiography, showed rapid and significant (p<0.05, n=5) decrease in fractional shortening, compromised ejection fraction, and increased left ventricular mass. Decreased respiratory control ratio (RCR) noted in isolated heart mitochondria (p<0.05, n=5), faster nitroxide radical decay in EPR spectroscopy (p<0.05, n=3), along with elevated lipid peroxidation (p<0.05, n=3), glutathione oxidation (p<0.05, n=4) and lactate (p<0.05, n=4) indicated mitochondrial dysfunction and oxidant stress. Microarray and QPCR detected early onset changes in 22 miRNAs (p<0.05, n=3) including elevated miRNA-15b. Over expression of miRNA15b in cardiomyocytes, resulted in compromised mitochondrial membrane potential (measured by TMRM fluorescence and JC-1 flow cytometry, p<0.05, n=4). Conclusions- Acute depletion of Dicer in adult mice results in miRNA-15b dependent mitochondrial dysfunction and oxidative stress which is followed by rapid loss of cardiac function.
Embargo: A three-year embargo was granted for this item.
Series/Report no.: 2012 Edward F. Hayes Graduate Research Forum. 26th
Keywords: microrna
cardiomyopathy
dicer
oxidative stress
Description: Biological Sciences: 3rd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
URI: http://hdl.handle.net/1811/51778
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