Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke

被引:68
作者
Xu, Huichun [1 ,2 ]
Tang, Yang [1 ,2 ]
Liu, Da-Zhi [1 ,2 ]
Ran, Ruiqiong [1 ,2 ]
Ander, Bradley P. [1 ,2 ]
Apperson, Michelle [1 ,2 ]
Liu, Xin She [1 ,2 ]
Khoury, Jane C. [3 ]
Gregg, Jeffrey P. [4 ]
Pancioli, Arthur [5 ]
Jauch, Edward C. [5 ]
Wagner, Kenneth R. [6 ]
Verro, Piero [1 ,2 ]
Broderick, Joseph P. [6 ]
Sharp, Frank R. [1 ,2 ]
机构
[1] Univ Calif Davis, MIND Inst, Sacramento, CA 95817 USA
[2] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA
[3] Univ Cincinnati, Med Ctr, Cincinnati Childrens Hosp, Cincinnati, OH 45267 USA
[4] Univ Calif Davis, Dept Pathol, Sacramento, CA 95817 USA
[5] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA
[6] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA
关键词
atherosclerosis; blood; embolic stroke; etiology; gene expression profiling; ischemic stroke;
D O I
10.1038/jcbfm.2008.22
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
There are no biomarkers that differentiate cardioembolic from large-vessel atherosclerotic stroke, although the treatments differ for each and similar to 30% of strokes and transient ischemic attacks have undetermined etiologies using current clinical criteria. We aimed to define gene expression profiles in blood that differentiate cardioembolic from large-vessel atherosclerotic stroke. Peripheral blood samples were obtained from healthy controls and acute ischemic stroke patients (< 3, 5, and 24 h). RNA was purified, labeled, and applied to Affymetrix Human U133 Plus 2.0 Arrays. Expression profiles in the blood of cardioembolic stroke patients are distinctive from those of large-vessel atherosclerotic stroke patients. Seventy-seven genes differ at least 1.5-fold between them, and a minimum number of 23 genes differentiate the two types of stroke with at least 95.2% specificity and 95.2% sensitivity for each. Genes regulated in large-vessel atherosclerotic stroke are expressed in platelets and monocytes and modulate hemostasis. Genes regulated in cardioembolic stroke are expressed in neutrophils and modulate immune responses to infectious stimuli. This new method can be used to predict whether a stroke of unknown etiology was because of cardioembolism or large-vessel atherosclerosis that would lead to different therapy. These results have wide ranging implications for similar disorders.
引用
收藏
页码:1320 / 1328
页数:9
相关论文
共 40 条
[1]   CLASSIFICATION OF SUBTYPE OF ACUTE ISCHEMIC STROKE - DEFINITIONS FOR USE IN A MULTICENTER CLINICAL-TRIAL [J].
ADAMS, HP ;
BENDIXEN, BH ;
KAPPELLE, LJ ;
BILLER, J ;
LOVE, BB ;
GORDON, DL ;
MARSH, EE ;
KASE, CS ;
WOLF, PA ;
BABIKIAN, VL ;
LICATAGEHR, EE ;
ALLEN, N ;
BRASS, LM ;
FAYAD, PB ;
PAVALKIS, FJ ;
WEINBERGER, JM ;
TUHRIM, S ;
RUDOLPH, SH ;
HOROWITZ, DR ;
BITTON, A ;
MOHR, JP ;
SACCO, RL ;
CLAVIJO, M ;
ROSENBAUM, DM ;
SPARR, SA ;
KATZ, P ;
KLONOWSKI, E ;
CULEBRAS, A ;
CAREY, G ;
MARTIR, NI ;
FICARRA, C ;
HOGAN, EL ;
CARTER, T ;
GURECKI, P ;
MUNTZ, BK ;
RAMIREZLASSEPAS, M ;
TULLOCH, JW ;
QUINONES, MR ;
MENDEZ, M ;
ZHANG, SM ;
ALA, T ;
JOHNSTON, KC ;
ANDERSON, DC ;
TARREL, RM ;
NANCE, MA ;
BUDLIE, SR ;
DIERICH, M ;
HELGASON, CM ;
HIER, DB ;
SHAPIRO, RA .
STROKE, 1993, 24 (01) :35-41
[2]   Sepsis and coagulation [J].
Aird, WC .
CRITICAL CARE CLINICS, 2005, 21 (03) :417-+
[3]   Inflammation as a risk factor for atrial fibrillation [J].
Aviles, RJ ;
Martin, DO ;
Apperson-Hansen, C ;
Houghtaling, PL ;
Rautaharju, P ;
Kronmal, RA ;
Tracy, RP ;
Van Wagoner, DR ;
Psaty, BM ;
Lauer, MS ;
Chung, MK .
CIRCULATION, 2003, 108 (24) :3006-3010
[4]   Bacterial adhesion on polyurethane surfaces conditioned with thrombus components [J].
Baumgartner, JN ;
Cooper, SL .
ASAIO JOURNAL, 1996, 42 (05) :M476-M479
[5]   Is atrial fibrillation an inflammatory disorder? [J].
Boos, CJ ;
Anderson, RA ;
Lip, GYH .
EUROPEAN HEART JOURNAL, 2006, 27 (02) :136-149
[6]  
Bruins P, 1997, CIRCULATION, V96, P3542
[7]  
Caplan LR, 2006, BRAIN EMBOLISM
[8]   Increased platelet CD63 and P-selectin expression persist in atherosclerotic ischemic stroke [J].
Cha, JK ;
Jo, WS ;
Shin, HC ;
Bae, HR ;
Ho, JM ;
Kim, JW .
PLATELETS, 2004, 15 (01) :3-7
[9]   Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation [J].
Conway, DSG ;
Buggins, P ;
Hughes, E ;
Lip, GYH .
AMERICAN HEART JOURNAL, 2004, 148 (03) :462-466
[10]   Inflammatory mechanisms after ischemia and stroke [J].
Danton, GH ;
Dietrich, WD .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2003, 62 (02) :127-136