Genomic and proteomic determinants of outcome in patients undergoing thoracoabdominal aortic aneurysm repair

被引:46
作者
Feezor, RJ
Baker, HV
Xiao, WH
Lee, WA
Huber, TS
Mindrinos, M
Kim, RA
Ruiz-Taylor, L
Moldawer, LL
Davis, RW
Seeger, JM
机构
[1] Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA
[2] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA
[3] Stanford Genome Technol Ctr, Palo Alto, CA 94305 USA
[4] Zyomyx, Hayward, CA 94545 USA
关键词
D O I
10.4049/jimmunol.172.11.7103
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Thoracoabdominal aortic aneurysm repair, with its requisite intraoperative mesenteric ischemia-reperfusion, often results in the development of systemic inflammatory response syndrome, multiorgan dysfunction syndrome (MODS), and death. In the present study, an adverse clinical outcome following thoracoabdominal aortic aneurysm repair was identified by blood leukocyte genomic and plasma proteomic responses. Time-dependent changes in the expression of 146 genes from blood leukocytes were observed (p < 0.001). Expression of 138 genes (p <.0.001) and the concentration of seven plasma proteins discriminated between patients who developed MODS and those who did not, and many of these differences were evident even before surgery. These findings suggest that changes in blood leukocyte gene expression and plasma protein concentrations can illuminate pathophysiological processes that are subsequently associated with the clinical sequelae of systemic inflammatory response syndrome and MODS. These changes in gene expression and plasma protein concentrations are often observed before surgery, consistent with either a genetic predisposition or pre-existing inflammatory state.
引用
收藏
页码:7103 / 7109
页数:7
相关论文
共 29 条
[1]   Why immunomodulatory therapies have not worked in sepsis [J].
Abraham, E .
INTENSIVE CARE MEDICINE, 1999, 25 (06) :556-566
[2]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[3]  
Bernard GR, 1995, AM J RESP CRIT CARE, V151
[4]   PLASMA-LEVELS OF THE CHEMOKINES MONOCYTE CHEMOTACTIC PROTEIN-1 AND PROTEIN-2 ARE ELEVATED IN HUMAN SEPSIS [J].
BOSSINK, AWJ ;
PAEMEN, L ;
JANSEN, PM ;
HACK, CE ;
THIJS, LG ;
VANDAMME, J .
BLOOD, 1995, 86 (10) :3841-3847
[5]   The outcome in the United States after thoracoabdominal aortic aneurysm repair, renal artery bypass, and mesenteric revascularization [J].
Derrow, AE ;
Seeger, JM ;
Dame, DA ;
Carter, RL ;
Ozaki, CK ;
Flynn, TC ;
Huber, TS .
JOURNAL OF VASCULAR SURGERY, 2001, 34 (01) :54-60
[6]   MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data [J].
Doniger, SW ;
Salomonis, N ;
Dahlquist, KD ;
Vranizan, K ;
Lawlor, SC ;
Conklin, BR .
GENOME BIOLOGY, 2003, 4 (01)
[7]   Cluster analysis and display of genome-wide expression patterns [J].
Eisen, MB ;
Spellman, PT ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14863-14868
[8]   THE ACUTE SPLANCHNIC AND PERIPHERAL TISSUE METABOLIC RESPONSE TO ENDOTOXIN IN HUMANS [J].
FONG, YM ;
MARANO, MA ;
MOLDAWER, LL ;
WEI, H ;
CALVANO, SE ;
KENNEY, JS ;
ALLISON, AC ;
CERAMI, A ;
SHIRES, GT ;
LOWRY, SF .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (06) :1896-1904
[9]   Transcription factor NFκB expression and postsurgical organ dysfunction [J].
Foulds, S ;
Galustian, C ;
Mansfield, AO ;
Schachter, M .
ANNALS OF SURGERY, 2001, 233 (01) :70-78
[10]   Visceral ischemia and neutrophil activation in sepsis and organ dysfunction [J].
Foulds, S ;
Mireskandari, M ;
Kalu, P ;
Jackson, W ;
Cheshire, NJ ;
Mansfield, AO ;
Schachter, M .
JOURNAL OF SURGICAL RESEARCH, 1998, 75 (02) :170-176