Background
White matter hyperintensity (WMH), a common radiographic finding associated with stroke
risk and outcome, has been linked to matrix metalloproteinase (MMP) activity and increased
levels of oxidative stress in nonstroke populations. We sought to determine whether
WMH severity is associated with plasma levels of MMPs and oxidative stress (F2-isoprostane)
in subjects with acute ischemic stroke (AIS).
Methods
We measured plasma biomarker levels at baseline and 48 hours in consecutive AIS subjects.
White matter hyperintensity volume (WMHv) was quantified on admission magnetic resonance
imaging using a validated semiautomated protocol, and Spearman correlation coefficients
were derived for all measured biomarkers.
Results
We enrolled 405 AIS subjects (mean age 70 ± 15 years; 58% male; median WMHv 3.4 cm3, interquartile range 1.4-9.5). WMHv and age were strongly correlated (ρ = .57, P < .0001). WMHv and MMP-2 levels were correlated at baseline (ρ = .23, P < .0001) and at 48 hours poststroke (ρ = .19, P = .002). In multivariate analysis, 48-hour MMP-2 levels were independently associated
with WMHv (β = .12, P = .04). MMP-9 and F2-isioprostane levels did not correlate with WMHv.
Conclusions
In AIS patients, MMP-2 levels are associated with the pre-existing burden of WMH.
If validated, these findings may further elucidate the role of MMP-2 in pathophysiology
of chronic cerebrovascular injury, such as WMH, and in brain susceptibility to acute
ischemia.
Key Words
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Article info
Publication history
Published online: January 21, 2014
Accepted:
November 3,
2013
Received in revised form:
October 27,
2013
Received:
July 30,
2013
Footnotes
Z.A.C. and N.S.R. contributed equally and share first authorship.
Sources of funding: Funding provided by the Sarnoff Cardiovascular Research Foundation (Z.A.C.); NIH SPOTRIAS grant P50NS051343 (K.L.F.); NIH National Institute of Neurological Disorders and Stroke (NINDS) K23NS064052 and R01NS082285 (N.S.R.); the American Stroke Association–Bugher Foundation (K.L.F., E.H.L., and N.S.R.); and The Deane Institute for Integrative Study of Atrial Fibrillation and Stroke at MGH (K.A. and K.L.F.).
Conflict of interest/disclosure: None.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.11.002
Copyright
© 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
