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Molecular Medicine

, Volume 17, Issue 5–6, pp 542–549 | Cite as

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

  • Bixi Jian
  • Shaolong Yang
  • Dongquan Chen
  • Luyun Zou
  • John C Chatham
  • Irshad Chaudry
  • Raghavan Raju
Research Article

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 Bnip3were increased, and Pgc1-α and Ppar-a a decreased following T-H. Eleven †RNA 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 transcrip-tional 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.

Notes

Acknowledgments

The study was supported by NIH grants AG 031440 (R Raju), GM 39519 (I Chaudry), HL101192, HL079364 and HL67464 (JC Chatham) and the UAB HSF GEF Scholar Award (R Raju). The microarray experiments were carried out in the Heflin Center for Genomic Science by Michael Crowley and supported by the UAB Comprehensive Cancer Center Core Grant 5P30 CA13148-37.

Supplementary material

10020_2011_1705542_MOESM1_ESM.pdf (1.2 mb)
Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Bixi Jian
    • 1
  • Shaolong Yang
    • 1
  • Dongquan Chen
    • 2
  • Luyun Zou
    • 3
  • John C Chatham
    • 3
  • Irshad Chaudry
    • 1
    • 4
  • Raghavan Raju
    • 1
    • 4
  1. 1.Center for Surgical Research, Department of SurgeryUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Clinical Translational Science Institute and Center for NeurosciencesWest Virginia UniversityMorgantownUSA
  3. 3.Department of Medicine, Division of Cardiovascular DiseaseUniversity of Alabama at BirminghamBirminghamUSA
  4. 4.Department of MicrobiologyUniversity of Alabama at BirminghamBirminghamUSA

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