Exercise training alters the molecular response to myocardial infarction

Purpose: We and others have shown that swimming exercise training performed before irreversible coronary occlusion improves the outcome of the heart injury and alters gene expression at the remodeling phase. The purpose of the current study was to identify temporal changes in the molecular response to myocardial infraction of prior exercise trained rats during the acute, the subacute, and the chronic phases postinfarction. Methods: Rats underwent a 7-wk swimming or sedentary protocol and were subjected to surgical induction of acute myocardial infarction (MI). Hearts were removed before and at 4 h, 2 d, and 4 wk after surgery. RNA extracted from the surviving myocardium of the MI hearts or from corresponding tissues in the non-MI hearts was subjected to multitranscript profiling. Results for representative transcripts were validated by reverse transcription and quantitative polymerase chain reaction amplification. Results: Global analysis of the 3686 detected transcripts generated a two-branch dendrogram that distinguished the pre-MI and the 4-h groups from the 2-d and the 4-wk groups and indicated that early after MI, the impact of infarction on the genes expressed overrides the training effect, whereas at 4 wk, the exercised hearts differ markedly from the nonexercised. Clustering the 1500 genes that showed the highest variance over time indicated differential expression of transcription regulators and proapoptotic genes 4 h and 2 d after MI and of stress-related and profibrotic genes 4 wk later in the exercised compared with sedentary hearts. Conclusion: Swimming exercise training conducted before acute MI reprograms the surviving myocardium for altered molecular response to MI that explains, in part, the protected cardiac phenotype of the exercised animals.