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 Pillai Raju

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 mito-chondrial 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-Mycand cardiac death promoting gene Bnip3were 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 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.

Original languageEnglish (US)
Pages (from-to)542-549
Number of pages8
JournalMolecular Medicine
Volume17
Issue number5-6
DOIs
StatePublished - May 1 2011
Externally publishedYes

Fingerprint

Mitochondrial Genes
Hemorrhage
Gene Expression
Wounds and Injuries
Cell Aging
Transfer RNA
Oligonucleotide Array Sequence Analysis
Mitochondrial DNA
Transcriptome
Resuscitation
Genes
Rodentia
Sepsis
Myocardium
Mitochondria
Transcription Factors

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Aging influences cardiac mitochondrial gene expression and cardiovascular function following hemorrhage injury. / Jian, Bixi; Yang, Shaolong; Chen, Dongquan; Zou, Luyun; Chatham, John C.; Chaudry, Irshad; Raju, Raghavan Pillai.

In: Molecular Medicine, Vol. 17, No. 5-6, 01.05.2011, p. 542-549.

Research output: Contribution to journalArticle

Jian, Bixi ; Yang, Shaolong ; Chen, Dongquan ; Zou, Luyun ; Chatham, John C. ; Chaudry, Irshad ; Raju, Raghavan Pillai. / Aging influences cardiac mitochondrial gene expression and cardiovascular function following hemorrhage injury. In: Molecular Medicine. 2011 ; Vol. 17, No. 5-6. pp. 542-549.
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