Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients.
OBJECTIVE
New insights in the pathophysiology of lacunar stroke (LS) suggest that it is caused by increased permeability of the blood-brain barrier due to endothelial activation. Because endothelial cells are the major production and storage site of tissue factor pathway inhibitor (TFPI), this protein can be used as marker of endothelial activation. In this observational study we measured the different pools of TFPI, as a marker of endothelial function, in first-ever lacunar stroke patients.


METHODS
We determined antigen levels of total and free full-length (FL) TFPI using ELISA in 149 patients and 42 controls. Heparin-releasable free FL TFPI was determined in a random subset of 17 patients and 15 controls. By brain MRI, we classified LS patients as having isolated lacunar infarct (ILA) or silent ischemic lesions (SILs).


RESULTS
Plasma levels of total TFPI were highest in patients with SILs compared with those with ILA, but this association disappeared after correction for age and levels of low-density lipoprotein cholesterol. However, levels of heparin-releasable free FL TFPI were higher in patients than in controls.


CONCLUSIONS
Although ambient plasma levels of total TFPI were not different in subtypes of LS, the increased levels of heparin-releasable TFPI in patients suggest a role of endothelial activation in the pathogenesis of LS.
Department of Neurology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, The Netherlands. i.knottnerus@mst.nl
I L H
IL
Knottnerus
K
K
Winckers
H
H
Ten Cate
T M
TM
Hackeng
J
J
Lodder
R P W
RP
Rouhl
J
J
Staals
J W P
JW
Govers-Riemslag
O
O
Bekers
R J
RJ
van Oostenbrugge
D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D015415:Biomarkers; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002985:Clinical Protocols; D003718:Denmark; D004730:Endothelium, Vascular / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008074:Lipoproteins / Q000378:metabolism*; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D059409:Stroke, Lacunar / Q000145:classification / Q000378:metabolism*
D000925:Anticoagulants; D015415:Biomarkers; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin