Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression

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Title Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression
Author Ashton, Kevin John; Holmgren, Kirsty; Peart, Jason Nigel John; Lankford, Amy R.; Matherne, G. Paul; Grimmond, Sean; Headrick, John Patrick
Journal Name Cardiovascular Research
Year Published 2003
Place of publication Netherlands
Publisher Elsevier Science
Abstract Objectives: To identify potential molecular genetic determinants of cardiovascular ischemic tolerance in wild-type and transgenic hearts overexpressing A1 adenosine receptors (A1ARs). Methods: cDNA microarrays were used to explore expression of 1824 genes in wild-type hearts and ischemia-tolerant mouse hearts overexpressing A1ARs. Results: Overexpression of A1ARs reduced post-ischemic contractile dysfunction, limited arrhythmogenesis, and reduced necrosis by 80% in hearts subjected to 30 min global ischemia 60 min reperfusion. Cardioprotection was abrogated by acute A1AR antagonism, and only a small number (19) of genes were modified by A1AR overexpression in normoxic hearts. Ischemia-reperfusion significantly altered expression of 75 genes in wild-type hearts (14 induced, 61 down-regulated), including genes for metabolic enzymes, structural/motility proteins, cell signaling proteins, defense/growth proteins, and regulators of transcription and translation. A1AR overexpression reversed the majority of gene down-regulation whereas gene induction was generally unaltered. Additionally, genes involved in cell defence, signaling and gene expression were selectively modified by ischemia in transgenic hearts (33 induced, 10 down-regulated), possibly contributing to the protected phenotype. Real-time PCR verified changes in nine selected genes, revealing concordance with array data. Transcription of the A1AR gene was also modestly reduced post-ischemia, consistent with impaired functional sensitivity to A1AR stimulation Conclusions: Data are presented regarding the early post-ischemic gene profile of intact heart. Reduced A1AR transcription is observed which may contribute to poor outcome from ischemia. A1AR overexpression selectively modifies post-ischemic gene expression, potentially contributing to ischemic-tolerance.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/S0008-6363(02)00738-1
Copyright Statement .
Volume 57
Page from 715
Page to 726
ISSN 0008-6363
Date Accessioned 2004-04-07
Date Available 2015-05-04T22:03:02Z
Language en_US
Research Centre Menzies Health Institute Qld; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Animal Physiology-Systems; PRE2009-Gene Expression
URI http://hdl.handle.net/10072/6132
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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