Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest.
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.


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 P< or =0.025 (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-1beta, 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.
Voisine
Pierre
P
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass 02215, USA.
Ruel
Marc
M
Khan
Tanveer A
TA
Bianchi
Cesario
C
Xu
Shu-Hua
SH
Kohane
Isaac
I
Libermann
Towia A
TA
Otu
Hasan
H
Saltiel
Alan R
AR
Sellke
Frank W
FW
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000368:Aged; D066258:Amphiregulin; D015152:Blotting, Northern; D015153:Blotting, Western; D002315:Cardiopulmonary Bypass; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000150:complications / Q000601:surgery*; D048909:Diabetes Complications / Q000235:genetics*; D054638:Dual Specificity Phosphatase 1; D066255:EGF Family of Proteins; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006324:Heart Arrest, Induced; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000209:etiology / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis / Q000235:genetics; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics; D012307:Risk Factors; D014158:Transcription, Genetic
C587848:AREG protein, human; D000199:Actins; D066258:Amphiregulin; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D066255:EGF Family of Proteins; D006023:Glycoproteins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C491294:PPP1R3C protein, human; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases