Off-pump coronary artery bypass surgery is associated with fewer gene expression changes in the human myocardium in comparison with on-pump surgery

Abstract

Ghorbel MT, Cherif M, Mokhtari A, Bruno VD, Caputo M, Angelini GD. Off-pump coronary artery bypass surgery is associated with fewer gene expression changes in the human myocardium in comparison with on-pump surgery. Physiol Genomics 42: 67-75, 2010. First published March 23, 2010 doi:10.1152/physiolgenomics.00174.2009.-Offpump coronary artery bypass surgery reduces the myocardial injury associated with on pump surgery with cardiopulmonary bypass (CPB) and ischemic-cardioplegic arrest (CA). We sought to find a mechanistic explanation for this by comparing the transcriptomic changes in the myocardium of patients undergoing on-and off-pump surgery. Transcriptomic analyses were performed on left ventricular biopsies obtained from patients prior to (pre-op) and after completion of all coronary anastomoses (post-op). Microarray results were validated with real-time polymerase chain reaction. In on-pump group, 68 genes were upregulated in post-op vs. pre-op biopsies (P Ͻ 0.01, Ն2-fold). They included inflammatory genes CCL3 and CCL4, apoptotic gene GADD45B and prostaglandin synthesis gene PTGS2 (COX-2). In the off-pump group, 17 genes were upregulated in post-op vs. pre-op biopsies (P Ͻ 0.01, Ն2-fold), all shared with on-pump patients. To uncover the genes implicated in CPB and ischemic-CA response, we compared the postoperative gene profiles of the two groups. Thirty-eight genes were upregulated in the on-pump vs. off-pump patients (P Ͻ 0.01, Ն2-fold). On-pump surgery induces injury-related response, as demonstrated by the upregulation of apoptosis and remodeling markers, whereas off-pump surgery ameliorates that by mainly upregulating a cytoprotective genetic program. Blood levels of the identified cytokines and chemokines followed the same pattern obtained by transcriptomics, suggesting that the myocardium is a likely source for these proteomic changes. In conclusion, offpump surgery is associated with fewer alterations in gene expression connected with inflammation, apoptosis, and remodeling seen after on-pump surgery with CPB and ischemic-CA.

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Transcriptome analysis defines myocardium gene signatures in children with ToF and ASD and reveals disease-specific molecular reprogramming in response to surgery with cardiopulmonary bypass

“…In the last years, several studies have demonstrated the value of myocardium transcriptome analysis for elucidating the molecular mechanisms underlying cardiovascular disease pathogenesis and identifying novel biomarkers for prognostic and therapeutic purposes [10,[13][14][15][16][17]30]. In this study, we carry out the first comparative gene expression profiling of ToF and ASD right atrial specimens before and after surgery with CPB.…”

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“…Studies that evaluated the circulating levels of proinflammatory cytokines (IL‐6, ‐8, and ‐10) after off‐ and on‐pump‐ surgery reported contradictory results 14, 18, 19, 20, 21, 22…”