Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium.
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 A(1), A(2A), A(2B), and A(3) 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 approximately 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 ( approximately 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 A(3) 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.
Ashton
Kevin J
KJ
Heart Foundation Research Centre, Griffith University Gold Coast, Southport, Qld 4217, Australia.
Nilsson
Ulrika
U
Willems
Laura
L
Holmgren
Kirsty
K
Headrick
John P
JP
D000222:Adaptation, Physiological; D000367:Age Factors; D000375:Aging; D000818:Animals; D046508:Culture Techniques; D005260:Female; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D007511:Ischemia / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D017725:Ventricular Pressure
D018047:Receptors, Purinergic P1