Genomic and proteomic determinants of outcome in patients undergoing thoracoabdominal aortic aneurysm repair.
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.
Feezor
Robert J
RJ
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Baker
Henry V
HV
Xiao
Wenzhong
W
Lee
W Anthony
WA
Huber
Thomas S
TS
Mindrinos
Michael
M
Kim
Raymond A
RA
Ruiz-Taylor
Laurence
L
Moldawer
Lyle L
LL
Davis
Ronald W
RW
Seeger
James M
JM
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000601:surgery*; D017545:Aortic Aneurysm, Thoracic / Q000601:surgery*; D001798:Blood Proteins / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology; D040901:Proteomics; D016896:Treatment Outcome
D001798:Blood Proteins