Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome.
BACKGROUND
Endothelial membrane microparticles (EMP) in plasma are elevated in several vascular diseases.


OBJECTIVE
To test the hypothesis that EMP would be increased in patients with acute ischemic stroke and would correlate with stroke severity, brain lesion volume and outcome.


METHODS
Forty-one patients were studied and divided into two groups based on the National Institutes of Health Stroke Scale (NIHSS) score: 20 patients with mild stroke (NIHSS score < 5) and 21 patients with moderate-severe stroke (NIHSS score > or = 5). Lesion volume was measured using diffusion-weighted magnetic resonance imaging and discharge outcome was based on the discharge Barthel and Rankin scores. Twenty-three age-matched control subjects were also studied. Using flow cytometry, endoglin-positive EMP: CD105+ CD41a-CD45- (E(+)EMP), specific endothelial EMP expressing VE-cadherin and endoglin: CD105+CD144+ (C(+)EMP), EMP expressing phosphatidylserine: CD105+PS+ CD41a- (PS(+)EMP) and EMP expressing ICAM-1: CD105+CD54+ CD45- (I(+)EMP) were analyzed.


RESULTS
Significantly higher PS(+)EMP counts were observed in the group of acute ischemic stroke patients [median 59 (25th-75th percentile: 28-86) MP microL(-1)] relative to the controls [28 (14-36) MP microL(-1)] (P = 0.002). All four EMP phenotypes studied were elevated in the subgroup of moderate-severe stroke patients relative to the controls (all P < 0.05). In the patients with acute ischemic stroke three EMP phenotypes (E(+)EMP, PS(+)EMP and I(+)EMP) correlated significantly with brain lesion volume, with I(+)EMP (P = 0.002) showing the strongest correlation. Admission counts of C(+)EMP (P = 0.0003) and E(+)EMP (P = 0.003) correlated significantly with discharge clinical outcome.


CONCLUSIONS
Certain circulating EMP phenotypes may be associated with severity, lesion volume and outcome of acute ischemic stroke. EMP analysis shows promising contribution to understanding stroke pathophysiology.
Simak
J
J
Laboratory of Cellular Hematology, CBER, FDA, HFM-335, Rockville, MD 20852-1448, USA. jan.simak@fda.hhs.gov
Gelderman
M P
MP
Yu
H
H
Wright
V
V
Baird
A E
AE
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood* / Q000628:therapy; D015820:Cadherins / Q000032:analysis; D016022:Case-Control Studies; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D010718:Phosphatidylserines / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood* / Q000473:pathology / Q000628:therapy; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D000071063:Endoglin; D018799:Intercellular Adhesion Molecule-1; D010718:Phosphatidylserines; D011956:Receptors, Cell Surface; D000099152:Cadherin 5; C064206:ENG protein, human