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(Circulation. 2004;110:II-280 – II-286.)
© 2004 American Heart Association, Inc.

Myocardial Protection and Vascular Biology

Differences in Gene Expression Profiles of Diabetic and Nondiabetic Patients Undergoing Cardiopulmonary Bypass and Cardioplegic Arrest

Pierre Voisine, MD; Marc Ruel, MD MPH; Tanveer A. Khan, MD; Cesario Bianchi, MD PhD; Shu-Hua Xu, PhD; Isaac Kohane, MD PhD; Towia A. Libermann, PhD; Hasan Otu, PhD; Alan R. Saltiel, PhD; Frank W. Sellke, MD

From Division of Cardiothoracic Surgery (P.V., T.A.K., C.B., S.-H.X., T.A.L., H.O., F.W.S.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass; the Division of Cardiac Surgery (M.R.), University of Ottawa Heart Institute, Ottawa, Canada; the Informatics Program (I.K.), Children’s Hospital, Harvard Medical School, Boston, Mass; Life Sciences Institute (A.R.S.), University of Michigan, Ann Arbor, Mich.

Correspondence to Frank W Sellke, MD, Chief, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, 110 Francis St., Suite 2A, Boston, MA 02215. E-mail fsellke{at}bidmc.harvard.edu

Background— Diabetes mellitus is an independent risk factor for early postoperative mortality and complications after coronary artery bypass grafting (CABG). We sought to compare the cardiac gene expression responses to cardiopulmonary bypass (CPB) and cardioplegic arrest (C) in patients with and without diabetes.

Methods and Results— Twenty atrial myocardium samples were harvested from 5 type II insulin-dependent diabetic and 5 matched nondiabetic patients undergoing CABG, before and after CPB/C. Oligonucleotide microarray analyses of 12625 genes were performed on the 10 sample pairs using matched pre-CPB tissues as controls. Array results were validated with Northern blotting and immunoblotting. Compared with pre-CPB/C, post-CPB/C myocardial tissues revealed 851 upregulated and 480 downregulated genes with a threshold P0.025 (signal-to-noise ratio, 4.04) in the diabetic group, compared with 480 upregulated and 626 downregulated genes (signal-to-noise ratio, 3.04) in the nondiabetic group (P<0.001). There were 18 genes that were upregulated >4-fold in diabetic and nondiabetic patients (including inflammatory/transcription activators FOS, CYR 61, and IL-6, apoptotic gene NR4A1, stress gene DUSP1, and glucose-transporter gene SLC2A3). However, 28 genes showed such marked upregulation in the diabetic group exclusively (including inflammatory/transcription activators MYC, IL8, IL-1ß, growth factor vascular endothelial growth factor, amphiregulin, and glucose metabolism-involved gene insulin receptor substrate 1), and 27 genes in the nondiabetic group only, including glycogen-binding subunit PPP1R3C.

Conclusions— Gene expression profile after CPB/C is quantitatively and qualitatively different in patients with diabetes. These results have important implications for the design of tailored myocardial protection and operative strategies for diabetic patients undergoing CPB/C.

Key Words: cardioplegia • cardiopulmonary bypass • complications • diabetes mellitus • genes