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Adenosine-induced cardiac gene expression of ischemic murine hearts revealed by cDNA array hybridization
Masanori Asakura1, Masafumi Kitakaze, Yasuhiko Sakata
1Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
Abstract:
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.
Insights
Investigating ischemic heart responses, this study found that adenosine receptor inhibition with 8-sulfophenyltheophylline (8SPT) modulated gene expression. 8SPT treatment normalized many genes altered by ischemic stress, highlighting adenosine
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Genomics
Background:
- Endogenous substances like adenosine play a role in ischemic heart disease pathophysiology.
- Understanding gene transcription changes during ischemia is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the transcriptional responses of murine hearts to ischemia.
- To determine the effect of adenosine receptor inhibition using 8-sulfophenyltheophylline (8SPT) on these transcriptional changes.
Main Methods:
- Murine hearts were subjected to ischemia for 60 minutes, with or without 8SPT administration.
- Messenger RNA (mRNA) was extracted for complementary DNA (cDNA) array analysis of gene expression.
- Analysis focused on both known and unknown genes modulated by ischemic stress and 8SPT treatment.
Main Results:
- Ischemia significantly modulated the expression of 24 known and 39 unknown genes.
- 8SPT treatment restored the expression levels of many upregulated and downregulated genes towards control levels.
- Significant upregulation (over 5-fold) was observed in 13 known and 32 unknown genes, with 8SPT normalizing these.
Conclusions:
- Cardiac gene expression is significantly modulated by ischemic stress.
- Endogenous adenosine influences the pathophysiology of ischemic hearts by modulating the expression of specific genes.
- Adenosine receptor inhibition presents a potential therapeutic avenue for managing ischemic heart conditions.