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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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 P≤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-1β, 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.

Original languageEnglish (US)
Pages (from-to)II280-II286
JournalCirculation
Volume110
Issue number11 SUPPL.
DOIs
StatePublished - Sep 14 2004

Fingerprint

Cardiopulmonary Bypass
Transcriptome
Genes
Signal-To-Noise Ratio
Coronary Artery Bypass
Down-Regulation
Insulin Receptor Substrate Proteins
Facilitative Glucose Transport Proteins
Microarray Analysis
Oligonucleotide Array Sequence Analysis
Glycogen
Interleukin-8
Interleukin-1
Immunoblotting
Northern Blotting
Vascular Endothelial Growth Factor A
Interleukin-6
Intercellular Signaling Peptides and Proteins
Myocardium
Diabetes Mellitus

Keywords

  • Cardioplegia
  • Cardiopulmonary bypass
  • Complications
  • Diabetes mellitus
  • Genes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Voisine, P., Ruel, M., Khan, T. A., Bianchi, C., Xu, S. H., Kohane, I., ... Sellke, F. W. (2004). Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest. Circulation, 110(11 SUPPL.), II280-II286. https://doi.org/10.1161/01.CIR.0000138974.18839.02

Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest. / Voisine, Pierre; Ruel, Marc; Khan, Tanveer A.; Bianchi, Cesario; Xu, Shu Hua; Kohane, Isaac; Libermann, Towia A.; Otu, Hasan; Saltiel, Alan R.; Sellke, Frank W.

In: Circulation, Vol. 110, No. 11 SUPPL., 14.09.2004, p. II280-II286.

Research output: Contribution to journalArticle

Voisine, P, Ruel, M, Khan, TA, Bianchi, C, Xu, SH, Kohane, I, Libermann, TA, Otu, H, Saltiel, AR & Sellke, FW 2004, 'Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest', Circulation, vol. 110, no. 11 SUPPL., pp. II280-II286. https://doi.org/10.1161/01.CIR.0000138974.18839.02
Voisine, Pierre ; Ruel, Marc ; Khan, Tanveer A. ; Bianchi, Cesario ; Xu, Shu Hua ; Kohane, Isaac ; Libermann, Towia A. ; Otu, Hasan ; Saltiel, Alan R. ; Sellke, Frank W. / Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest. In: Circulation. 2004 ; Vol. 110, No. 11 SUPPL. pp. II280-II286.
@article{a52f6a1ef07a4f8f9b4eb0341451470f,
title = "Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest",
abstract = "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 P≤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-1β, 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.",
keywords = "Cardioplegia, Cardiopulmonary bypass, Complications, Diabetes mellitus, Genes",
author = "Pierre Voisine and Marc Ruel and Khan, {Tanveer A.} and Cesario Bianchi and Xu, {Shu Hua} and Isaac Kohane and Libermann, {Towia A.} and Hasan Otu and Saltiel, {Alan R.} and Sellke, {Frank W.}",
year = "2004",
month = "9",
day = "14",
doi = "10.1161/01.CIR.0000138974.18839.02",
language = "English (US)",
volume = "110",
pages = "II280--II286",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "11 SUPPL.",

}

TY - JOUR

T1 - Differences in gene expression profiles of diabetic and nondiabetic patients undergoing cardiopulmonary bypass and cardioplegic arrest

AU - Voisine, Pierre

AU - Ruel, Marc

AU - Khan, Tanveer A.

AU - Bianchi, Cesario

AU - Xu, Shu Hua

AU - Kohane, Isaac

AU - Libermann, Towia A.

AU - Otu, Hasan

AU - Saltiel, Alan R.

AU - Sellke, Frank W.

PY - 2004/9/14

Y1 - 2004/9/14

N2 - 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 P≤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-1β, 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.

AB - 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 P≤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-1β, 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.

KW - Cardioplegia

KW - Cardiopulmonary bypass

KW - Complications

KW - Diabetes mellitus

KW - Genes

UR - http://www.scopus.com/inward/record.url?scp=4644338086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644338086&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000138974.18839.02

DO - 10.1161/01.CIR.0000138974.18839.02

M3 - Article

C2 - 15364876

AN - SCOPUS:4644338086

VL - 110

SP - II280-II286

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 11 SUPPL.

ER -