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Early Gene Expression Profiles During Intraoperative Myocardial Ischemia-Reperfusion in Cardiac Surgery

ABSTRACT: Right ventricular samples were serially acquired during surgical repair of ventricular septal defect. Expression profiling revealed three patterns of gene expression: (1) increased expression above control levels within one hour of cardioplegic arrest, with further amplification during early reperfusion; (2) increased expression limited to the reperfusion phase; and (3) reduced expression during reperfusion. Keywords: VSD Patients

ORGANISM(S): Homo sapiens

PROVIDER: GSE6381 | GEO | 2007/11/19

SECONDARY ACCESSION(S): PRJNA99553

REPOSITORIES: GEO

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Project description:Diet induced obesity in swine was associated with altered cardiovascular functional, miR transcriptome, and proteomic response to ischemia-reperfusion. Furthermore, the GLP-1 mimetic exendin-4 altered functional, miR and protein responses differently in obese versus lean swine, demonstrating the pervasive effect of obesity on modulating cardiac response to pathophysiologies and therapeutics. This study tested the hypothesis that obesity alters the left ventricular microRNA (miR) transcriptome, proteome and functional cardiac response to ischemia-reperfusion (I/R) injury and to glucagon like peptide-1 (GLP-1) receptor activation. Ossabaw swine were fed normal chow or obesogenic diet for 6 months followed by IV infusion of either saline (vehicle) or the GLP-1 mimetic exendin-4 (Ex-4). Left ventricular pressure volume relationships were assessed under baseline conditions, during a 30-minute occlusion of the circumflex artery and during a 2 hour reperfusion period. Cardiac biopsies were obtained from normally-perfused and ischemia-reperfusion territories, and analyzed using Affymetrix 3.0 miR microarray and protein mass spectrometry. I/R was found to depress global cardiac function in lean swine (systolic pressure, end-diastolic volume). In contrast, Ex-4 therapies did not affect blood pressure in obese animals, but significantly reduced end-diastolic volume following the reperfusion period. These divergent physiologic response to regional I/R in obese vs lean hearts were associated with significantly different protein and miRNA changes. Obesity was associated with altered abundance of proteins associated with calcium handling and contractility, and with changes in miRs relating to metabolism, hypertrophy, and cell death, including the miR-15 and miR-30 families, miR-199a, and miR-214. These effects were modified differently by EX-4 treatment in lean vs obese swine. These findings suggest specific miR and proteomic differences contribute to differences in functional cardiac responses to ischemia-reperfusion injury and pharmacologic activation of GLP-1 signaling in the setting of obesity, volume, stroke volume and ejection fraction) with partial amelioration seen in Ex-4 treated animals.

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Early Gene Expression Profiles During Intraoperative Myocardial Ischemia-Reperfusion in Cardiac Surgery

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