Endothelial activation in lacunar stroke subtypes.
OBJECTIVE
Lacunar stroke (LS) can be subtyped according to the absence (isolated lacunar infarct [ILA]) or presence of concomitant white matter lesions (WML) and/or asymptomatic lacunar infarcts. Endothelial activation is thought to play a pivotal role in the subtype with WML and/or asymptomatic lacunar infarcts. The aim of this study was to evaluate whether endothelial activation is associated with WML and/or asymptomatic lacunar infarcts in LS patients. Here, we determined levels of circulating blood markers of endothelial function in LS patients.


METHODS
In 149 patients, all of whom had brain-MRI, levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA-PAI-1 complex, von Willebrand factor, tissue factor, thrombomodulin, and coagulation factor VIII were determined. Levels of blood markers were related to subtypes of LS and adjusted for age, gender, and vascular risk factors.


RESULTS
In subtypes of LS, tPA activity was increased in patients with WML (0.79 IU/mL vs 0.44 IU/mL for ILA; P=0.02) and PAI-1-antigen levels were lowest in patients with WML (27.5 ng/mL vs 44.0 ng/mL for ILA; P=0.02). The association between WML and PAI-1 remained significant after multivariable analysis (OR, 0.99; 95% CI, 0.98-1.00 per ng/mL change of PAI-1; P=0.04).


CONCLUSIONS
We found further evidence for the hypothesis of endothelial activation in the subtype of LS caused by a diffuse small vessel vasculopathy, as we found higher levels of tPA in patients with concomitant extensive WML than in those with ILA. Second, low levels of PAI-1 were associated with WML. We postulate that differences in activity of components of the fibrinolytic system might contribute to WML development.
Knottnerus
Iris L H
IL
Department of Neurology, Maastricht University Medical Centre, Maastricht, the Netherlands. iris.knottnerus@home.nl
Govers-Riemslag
Jose W P
JW
Hamulyak
Karly
K
Rouhl
Rob P W
RP
Staals
Julie
J
Spronk
Henri M H
HM
van Oerle
Rene
R
van Raak
Elisabeth P M
EP
Lodder
Jan
J
ten Cate
Hugo
H
van Oostenbrugge
Robert J
RJ
D000368:Aged; D001921:Brain / Q000503:physiopathology*; D020520:Brain Infarction / Q000097:blood / Q000145:classification / Q000503:physiopathology*; D004727:Endothelium / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking; D018709:Statistics, Nonparametric; D018180:Thrombomodulin / Q000097:blood; D013925:Thromboplastin / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D014841:von Willebrand Factor; D005169:Factor VIII; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator