Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium

Kevin J. Ashton, Ulrika Nilsson, Laura Willems, Kirsty Holmgren, John P. Headrick

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28 Citations (Scopus)

Abstract

The well-documented age-related change in ischemic tolerance may result from impaired adenosine-mediated cardioprotection. Additionally, ischemia itself may potentially modify adenosine signalling, contributing to the post-ischemic phenotype. This study investigates age- and ischemia-dependent changes in adenosine receptor transcript levels (Adora) for the A1, A2A, A2B, and A3 receptor subtypes in mouse myocardium. Hearts from young (2-4 months) and moderately aged (16-18 months) mice were subjected to 20-min ischemia and 45-min reperfusion. Ischemic tolerance was impaired in aged hearts, which recovered less than 30% ventricular pressure development (compared with ∼70% in young hearts), and lost 2-fold higher levels of lactate dehydrogenase during reperfusion (reflecting cellular disruption). Real-time PCR analyses revealed an age-related decline in Adora3 levels and induction of Adora2B. Curiously, this effect was mimicked by ischemia, which acutely reduced Adora3 levels and induced Adora2B in young (but not old) hearts. In contrast, in aged hearts ischemia selectively reduced levels of Adora1 transcript (∼2-fold) without altering transcript levels for the other receptors. These results demonstrate selective modulation of cardioprotective adenosine receptor transcription by both aging and ischemia. Reduced A3 adenosine receptor transcription may contribute to impaired ischemic tolerance in aged hearts, whereas changes in Adora transcription induced by ischemia may impact on the post-ischemic phenotype at later time points.

Original languageEnglish
Pages (from-to)367-372
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume312
Issue number2
DOIs
Publication statusPublished - 2003
Externally publishedYes

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Purinergic P1 Receptors
Transcription
Myocardium
Ischemia
Aging of materials
Adenosine
Adenosine A3 Receptors
Reperfusion
Phenotype
L-Lactate Dehydrogenase
Ventricular Pressure
Real-Time Polymerase Chain Reaction
Modulation

Cite this

Ashton, Kevin J. ; Nilsson, Ulrika ; Willems, Laura ; Holmgren, Kirsty ; Headrick, John P. / Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 312, No. 2. pp. 367-372.
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Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium. / Ashton, Kevin J.; Nilsson, Ulrika; Willems, Laura; Holmgren, Kirsty; Headrick, John P.

In: Biochemical and Biophysical Research Communications, Vol. 312, No. 2, 2003, p. 367-372.

Research output: Contribution to journalArticleResearchpeer-review

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