Gene Expression in Peripheral Blood Differs after Cardioembolic Compared with Large-Vessel Atherosclerotic Stroke: Biomarkers for the Etiology of Ischemic Stroke

Abstract

There are no biomarkers that differentiate cardioembolic from large-vessel atherosclerotic stroke, although the treatments differ for each and B30% 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.

Blood Biomarkers of Ischemic Stroke

“…RNAwas isolated from blood and run on Affymetrix U133 Plus2.0 microarrays. In 33 samples from 11 patients, a 23 gene panel distinguished cardioembolic from large vessel ischemic stroke with >95% sensitivity and specificity [41]. In a larger study of 194 samples from 76 acute ischemic strokes, a 40 gene panel was able to distinguish cardioembolic from large vessel ischemic stroke with >95% sensitivity and specificity at each of 3 hours, 5 hours, and 24 hours after stroke onset [42].…”

Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction

“…PDGFA is observed to be involved in atherosclerotic stroke previously (Xu et al, 2008). PDGF signaling is also reported to regulate blood-brain barrier permeability and integrity during ischemic stroke (Su et al, 2008).…”

Correlation of Adrenomedullin gene expression in peripheral blood leukocytes with severity of ischemic stroke

“…Thus, far there are over 58 proteins and 7 panels of proteins which have been described to possess the features to be potential biomarkers for the diagnosis and prognosis of ischemic stroke [30][31][32][33]. However, several studies have described the possibility of using peripheral blood gene expression in the diagnosis in stroke [34][35][36], and the advantages of using a RNA biomarker in stroke have also been considered. Gene transcription is affected by stroke rapidly; it can occur within minutes, whereas protein translation occurs later than gene transcription.…”