Adenosine-mediated cardioprotection in the aging myocardium.
With aging, it appears the heart's ability to withstand injury declines markedly. Unfortunately, the incidence of ischemic disorders increases dramatically with age. Though the genesis of the ischemia-intolerant phenotype is incompletely understood (and likely multi-factorial), it may involve changes in intrinsic cardioprotective responses. In this respect we and others have interrogated the role of the adenosine receptor (AR) system in dictating ischemic tolerance and the impact of age on AR-mediated cardioprotection. It is intriguing to note ARs impact on many processes implicated in myocardial 'aging': adenosine counters Ca2+ influx and oxidant injury, modifies substrate metabolism to improve tolerance, is pro-angiogenic, inhibits myocardial fibrosis, and can limit apoptosis. Thus, dysregulation of the AR system could contribute to many features of aged hearts (including ischemic intolerance). The latter is borne out by observations that AR-mediated protective responses decline with intrinsic tolerance and that transgenic manipulation of the AR system restores intrinsic tolerance and protective responses in aged hearts. Mechanisms underlying failure in adenosinergic protection remain undefined. Here we review data on the effects of aging on cardiovascular AR transcription and expression, generation of signal (adenosine formation), and protective signaling coupled to ARs.
Willems
Laura
L
Heart Foundation Research Centre, School of Health Science, Griffith University, Southport, QLD 4217, Australia.
Ashton
Kevin J
KJ
Headrick
John P
JP
D000241:Adenosine / Q000502:physiology*; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D010740:Phospholipases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D000975:Antioxidants; D018047:Receptors, Purinergic P1; D011493:Protein Kinase C; D010740:Phospholipases; D000241:Adenosine