Adenosine-mediated cardioprotection in the aging myocardium

Laura Willems, Kevin J. Ashton, John P. Headrick

Research output: Contribution to journalReview articleResearchpeer-review

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)245-255
Number of pages11
JournalCardiovascular Research
Volume66
Issue number2
DOIs
Publication statusPublished - 1 May 2005
Externally publishedYes

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Purinergic P1 Receptors
Adenosine
Myocardium
Wounds and Injuries
Oxidants
Fibrosis
Ischemia
Apoptosis
Phenotype
Incidence

Cite this

Willems, Laura ; Ashton, Kevin J. ; Headrick, John P. / Adenosine-mediated cardioprotection in the aging myocardium. In: Cardiovascular Research. 2005 ; Vol. 66, No. 2. pp. 245-255.
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Adenosine-mediated cardioprotection in the aging myocardium. / Willems, Laura; Ashton, Kevin J.; Headrick, John P.

In: Cardiovascular Research, Vol. 66, No. 2, 01.05.2005, p. 245-255.

Research output: Contribution to journalReview articleResearchpeer-review

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