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Physiol. Genomics 25: 364-374, 2006. First published March 22, 2006; doi:10.1152/physiolgenomics.00013.2006
1094-8341/06 $8.00
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Received 27 January 2006; accepted in final form 3 March 2006.
Physiological Genomics 25:364-374 (2006)
1094-8341/06 $8.00 © 2006 American Physiological Society

Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix

Sashwati Roy1, Savita Khanna1, Donald E. Kuhn1, Cameron Rink1, Willis T. Williams1, Jay L. Zweier2 and Chandan K. Sen1

1 Laboratory of Molecular Medicine, Department of Surgery Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio
2 Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio

cDNA microarray analysis was performed to screen 15,000 genes and expressed sequence tags (ESTs) to identify changes in the ischemia-reperfused (I-R) rat myocardial transcriptome in the early (day 2) and late (day 7) inflammatory phases of acute myocardial infarction. Lists of candidate genes that were affected by I-R transiently (2 or 7 days only) or on a more sustained basis (2 and 7 days) were derived. The candidate genes represented three major functional categories: extracellular matrix, apoptosis, and inflammation. To expand on the findings from microarray studies that dealt with the two above-mentioned time points, tissues collected from days 0, 0.25, 2, 3, 5, and 7 after reperfusion were examined. Acute myocardial infarction resulted in upregulation of IL-6 and IL-18. Genes encoding extracellular matrix proteins such as types I and III collagen were upregulated in day 2, and that response progressively grew stronger until day 7 after I-R. Comparable response kinetics was exhibited by the candidate genes of the apoptosis category. Caspases-2, -3, and -8 were induced in response to acute infarction. Compared with the myocardial tissue from the sham-operated rats, tissue collected from the infarct region stained heavily positive for the presence of active caspase-3. Laser microdissection and pressure catapulting technology was applied to harvest infarct and adjacent noninfarct control tissue from a microscopically defined region in the rat myocardium. Taken together, this work presents the first evidence gained from the use of DNA microarrays to understand the molecular mechanisms implicated in the early and late inflammatory phases of the I-R heart.

heart; oxygen; perceived hyperoxia; wound healing




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