Age-associated shifts in cardiac gene transcription and transcriptional responses to ischemic stress
Ashton, Kevin J., Willems, Laura, Holmgren, Kirsty, Ferreira, Linda, and Headrick, John P. (2006) Age-associated shifts in cardiac gene transcription and transcriptional responses to ischemic stress. Experimental Gerontology, 41 (2). pp. 189-204.
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Aged hearts exhibit reduced tolerance to ischemia-reperfusion, together with altered structure and post-ischemic remodelling. The molecular bases of such changes are unclear. Using cDNA microarrays and quantitative RT-PCR we characterized shifts in gene expression patterns with aging in normoxic and post-ischemic (20 min global ischemia, 60 min reperfusion) murine hearts (young: 2–4 months; aged: 16–18 months). We identified an age-associated up-regulation of transcripts involved in cell death, oxygen transport and metabolism in normoxic hearts. Down-regulated transcripts were involved in transporter activity, protein binding and hydrolase activity, changes in MAPK, WNT and TGF-β signalling with aging were also observed. Ischemic stress generated a much greater degree of contractile impairment and cellular damage in aged vs. young hearts. This was associated with a substantially modified transcriptional response, with selective changes in Ca2+, WNT, NOTCH and G-protein coupled receptor signalling paths in aged vs. young hearts. Despite some common responses to ischemia in young and aged hearts (induction of heat shock protein transcripts), aging selectively modified ischemic responses of immediate early genes, and genes involved in modulating apoptosis and remodelling/angiogenesis. In summary, aging is associated with shifts in cardiovascular gene expression consistent with the phenotypic features of older hearts. Reduced tolerance with age may be related to modification of signalling (particularly WNT and TGF-β), and shifts in expression of immediate early genes, and genes important in control of cell death/survival, angiogenesis, and cardiac remodelling.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||aging; cDNA microarray; gene expression; ischemia-reperfusion|
|Date Deposited:||19 Apr 2010 04:35|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 50%
06 BIOLOGICAL SCIENCES > 0606 Physiology > 060699 Physiology not elsewhere classified @ 50%
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970102 Expanding Knowledge in the Physical Sciences @ 50%