Adenosine-induced cardiac gene expression of ischemic murine hearts revealed by cDNA array hybridization.

Because many endogenous substances, including adenosine, contribute to the pathophysiology of ischemic hearts, the present study was designed to investigate the transcription responses of murine hearts to ischemia with or without administration of an inhibitor of adenosine receptor, 8-sulfophenyltheophylline (8SPT). Sixty minutes after ligation of the proximal site of the left coronary artery with (n=9) or without (n=9) 8SPT, the hearts were excised to obtain mRNA for cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10-fold, and 11 known genes were upregulated 5.0-9.9-fold. 8SPT reduced the expressed gene to the control levels. Furthermore, 32 unknown genes were also upregulated over 5.0-fold. In contrast, 11 known genes were downregulated below 0.2-fold, and 64% of the downregulated genes were restored by 8SPT. The 7 unknown genes were downregulated to levels below 0.2-fold. Therefore, it was concluded that the cardiac expression of 24 known and 39 unknown genes was modulated by ischemic stress, and that these genes appeared to be related to the pathophysiology of the ischemic heart because endogenous adenosine modulated their expression.