Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment.
OBJECTIVE
Uncontrolled expression of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation. In animal models of cerebral ischemia, the expression of MMP-2 and MMP-9 was significantly increased. However, their role in human stroke in vivo remains unknown. Therefore, we sought to determine the temporal profile of MMP expression in patients with acute ischemic stroke and to investigate its relationship to stroke severity, location of arterial occlusion, and total infarct volume.


METHODS
Serial MMP-2 and MMP-9 determinations were made in 39 patients with cardioembolic strokes that involved the middle cerebral artery territory by means of enzyme-linked immunosorbent assay. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 12, 24, and 48 hours after stroke onset. Infarct volume was measured with CT scanning at 48 hours.


RESULTS
No correlation was found between MMP-2 and NIHSS score at any time point, although a close relation appeared between mean MMP-9 and final NIHSS score (r=0.486, P=0.002). MMP-9 value was the only factor associated with the final NIHSS score in the multiple logistic regression model (OR 4.54, 95% CI 1.5 to 13.75). A cut-point of MMP-9 142.18 ng/mL had a positive predictive value of 94.4% to assess a patient's NIHSS (<8 or >/=8) by the end of the study. Final MMP-2 and MMP-9 levels were significantly lower when recanalization occurred (528+/-144.3 versus 681.4+/-239.2 ng/mL, P=0.031 for MMP-2; 110.2+/-100.9 versus 244.8+/-130 ng/mL, P=0.004 for MMP-9). A positive correlation was found between mean MMP-9 and infarct volume (r=0.385, P=0.022).


CONCLUSIONS
MMPs are involved in the acute phase of human ischemic stroke. MMP-9 levels are associated with neurological deficit, middle cerebral artery occlusion, and infarct volume.
Montaner
J
J
Cerebrovascular Unit, Hemostasia Research Unit, Vall d'Hebron Hospital, Barcelona, Spain. alsa@hg.vhebron.es
Alvarez-Sabín
J
J
Molina
C
C
Anglés
A
A
Abilleira
S
S
Arenillas
J
J
González
M A
MA
Monasterio
J
J
D000208:Acute Disease; D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000175:diagnosis / Q000201:enzymology*; D016015:Logistic Models; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging; D011446:Prospective Studies; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications / Q000175:diagnosis / Q000201:enzymology*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D017585:Ultrasonography, Doppler, Transcranial
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9