Cardioprotection via preserved mitochondrial structure and function in the mPer2-mutant mouse myocardium

Jitka A. I Virag; Ethan J Anderson; Susan D Kent; Harrison D Blanton; Tracy L Johnson; Fatiha Moukdar; Jonathan H DeAntonio; Kathleen Thayne; Jian M Ding; Robert M Lust

doi:10.1152/ajpheart.00914.2012

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Cardioprotection via preserved mitochondrial structure and function in the mPer2-mutant mouse myocardium

Journal article

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Cardioprotection via preserved mitochondrial structure and function in the mPer2-mutant mouse myocardium

Jitka A. I Virag, Ethan J Anderson, Susan D Kent, Harrison D Blanton, Tracy L Johnson, Fatiha Moukdar, Jonathan H DeAntonio, Kathleen Thayne, Jian M Ding and Robert M Lust

American journal of physiology. Heart and circulatory physiology, Vol.305(4), pp.H477-H483

Mitochondria in Cardiovascular Physiology and Disease

08/15/2013

DOI: 10.1152/ajpheart.00914.2012

PMCID: PMC3891252

PMID: 23771689

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Abstract

We have previously shown that myocardial infarct size in nonreperfused hearts of mice with a functional deletion of the circadian rhythm gene mPer2 (mPer2-M) was reduced by 43%. We hypothesized that acute ischemia-reperfusion injury (I/R = 30 min I/2 h R) would also be reduced in these mice and that ischemic preconditioning (IPC) (3 × 5 min cycles) before I/R, which enhances protection in wild-type (WT) hearts, would provide further protection in mPer2-M hearts. We observed a 69 and 75% decrease in infarct size in mPer2-M mouse hearts compared with WT following I/R and IPC, respectively. This was coincident with 67% less neutrophil infiltration and 57% less apoptotic cardiomyocytes. IPC in mPer2-M mice before I/R had 48% less neutrophil density and 46% less apoptosis than their WT counterparts. Macrophage density was not different between WT and mPer2-M I/R, but it was 45% higher in mPer2-M IPC mouse hearts compared with WT IPC. There were no baseline differences in cardiac mitochondrial function between WT and mPer2-M mice, but, following I/R, WT exhibited a marked decrease in maximal O 2 consumption supported by complex I-mediated substrates, whereas mPer2-M did not, despite no difference in complex I content. Moreover, cardiac mitochondria from WT mice exhibited a very robust increase in ADP-stimulated O 2 consumption in response to exogenously added cytochrome c , along with a high rate of reactive oxygen species production, none of which was exhibited by cardiac mitochondria from mPer2-M following I/R. Taken together, these findings suggest that mPer2 deletion preserves mitochondrial membrane structure and functional integrity in heart following I/R injury, the consequence of which is preservation of myocardial viability. Understanding the mechanisms connecting cardiac events, mitochondrial function, and mPer2 could lead to preventative and therapeutic strategies for at risk populations.

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circadian

mitochondrial function

ischemia-reperfusion

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Details

Title: Subtitle: Cardioprotection via preserved mitochondrial structure and function in the mPer2-mutant mouse myocardium
Creators: Jitka A. I Virag - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Ethan J Anderson - Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina
Susan D Kent - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Harrison D Blanton - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Tracy L Johnson - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Fatiha Moukdar - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Jonathan H DeAntonio - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Kathleen Thayne - Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, North Carolina
Jian M Ding - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Robert M Lust - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.305(4), pp.H477-H483
Series: Mitochondria in Cardiovascular Physiology and Disease
DOI: 10.1152/ajpheart.00914.2012
PMID: 23771689
PMCID: PMC3891252
NLM abbreviation: Am J Physiol Heart Circ Physiol
ISSN: 0363-6135
eISSN: 1522-1539
Publisher: American Physiological Society; Bethesda, MD
Language: English
Date published: 08/15/2013
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
Record Identifier: 9984065312002771

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