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

Ashton, K. J., Holmgren, K., Peart, J., Lankford, A. R., Matherne, G. P., Grimmond, S. and Headrick, J. P. (2003) Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression. Cardiovascular Research, 57 3: 715-726. doi:10.1016/S0008-6363(02)00738-1


Author Ashton, K. J.
Holmgren, K.
Peart, J.
Lankford, A. R.
Matherne, G. P.
Grimmond, S.
Headrick, J. P.
Title Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression
Formatted title
Effects of A1 adenosine receptor overexpression on normoxic and post-ischemic gene expression
Journal name Cardiovascular Research   Check publisher's open access policy
ISSN 0008-6363
Publication date 2003-03-01
Sub-type Article (original research)
DOI 10.1016/S0008-6363(02)00738-1
Volume 57
Issue 3
Start page 715
End page 726
Total pages 12
Editor M. J. Janse
Place of publication Amsterdam
Publisher Elsevier BV
Collection year 2003
Language eng
Subject C1
270201 Gene Expression
730106 Cardiovascular system and diseases
Abstract Objectives: To identify potential molecular genetic determinants of cardiovascular ischemic tolerance in wild-type and transgenic hearts overexpressing A(1) adenosine receptors (A(1)ARs). Methods: cDNA microarrays were used to explore expression of 1824 genes ill wild-type hearts and ischemia-tolerant mouse hearts overexpressing A(1)ARs. Results: Overexpression of A(1)ARs reduced post-ischemic contractile dysfunction, limited arrhythmogenesis, and reduced necrosis by similar to80% in hearts subjected to 30 min global ischemia 60 mill reperfusion. Cardioprotection was abrogated by acute A(1)AR antagonism, and only a small number (19) of genes were modified by A(1)AR 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. A(1)AR 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 A(1)AR gene was also modestly reduced post-ischemia, consistent with impaired functional sensitivity to A(1)AR stimulation Conclusions: Data are presented regarding the early post-ischemic gene profile of intact heart. Reduced A(1)AR transcription is observed which may contribute to poor outcome from ischemia. A(1)AR overexpression selectively modifies post-ischemic gene expression, potentially contributing to ischemic-tolerance. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
Keyword Cardiac & Cardiovascular Systems
Adenosine
Gene Expression
Ischemia
Receptors
Reperfusion
Working Rat Hearts
Mouse Heart
Myocardium
Microarray
Protein
Cardioprotection
Identification
Inhibition
Metabolism
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 02:47:39 EST