Abstract
Cardiac dysfunction and mortality associated with trauma and sepsis increase with age. Mitochondria play a critical role in the energy demand of cardiac muscles, and thereby on the function of the heart. Specific molecular pathways responsible for mitochondrial functional alterations after injury in relation to aging are largely unknown. To further investigate this, 6- and 22-month-old rats were subjected to trauma-hemorrhage (T-H) or sham operation and euthanized following resuscitation. Left ventricular tissue was profiled using our custom rodent mitochondrial gene chip (RoMitochip). Our experiments demonstrated a declined left ventricular performance and decreased alteration in mitochondrial gene expression with age following T-H and we have identified c-Myc, a pleotropic transcription factor, to be the most upregulated gene in 6- and 22-month-old rats after T-H. Following T-H, while 142 probe sets were altered significantly (39 up and 103 down) in 6-month-old rats, only 66 were altered (30 up and 36 down) in 22-month-old rats; 36 probe sets (11 up and 25 down) showed the same trend in both groups. The expression of c-Myc and cardiac death promoting gene Bnip3 were increased, and Pgc1-α and Ppar-α a decreased following T-H. Eleven tRNA transcripts on mtDNA were upregulated following T-H in the aged animals, compared with the sham group. Our observations suggest a c-myc-regulated mitochondrial dysfunction following T-H injury and marked decrease in age-dependent changes in the transcriptional profile of mitochondrial genes following T-H, possibly indicating cellular senescence. To our knowledge, this is the first report on mitochondrial gene expression profile following T-H in relation to aging.
Highlights
Bixi Jian University of Alabama, Birmingham Shaolong Yang University of Alabama, Birmingham Dongquan Chen West Virginia University Lunyun Zou University of Alabama, Birmingham John C
We report our findings on mitochondrial gene expression changes in rat cardiomyocytes subjected to in vitro hypoxia and age-dependent cardiac mitochondrial gene expression changes in an in vivo model of T-H
T-H resulted in increased plasma lactate and decreased mean arterial pressure as compared with sham controls in both age groups
Summary
Bixi Jian University of Alabama, Birmingham Shaolong Yang University of Alabama, Birmingham Dongquan Chen West Virginia University Lunyun Zou University of Alabama, Birmingham John C. Authors Bixi Jian, Shaolong Yang, Dongquan Chen, Lunyun Zou, John C. The molecular mechanism of mitochondrial damage and dysfunction to cardiomyocytes and its contribution to the outcome of T-H in relation to aging are not fully known. Tory complex, was found to be reduced significantly, along with an increase in cytosolic cytochrome c levels, decrease in mitochondrial ATP levels and increased cardiomyocyte apoptosis [5]. A prolonged depression of cardiovascular function following T-H, despite fluid resuscitation was reported by other investigators [8,9,10]
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