White matter hyperintensity volume correlates with matrix metalloproteinase-2 in acute ischemic stroke

J Stroke Cerebrovasc Dis. 2014 Jul;23(6):1300-6. doi: 10.1016/j.jstrokecerebrovasdis.2013.11.002. Epub 2014 Jan 16.


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.

Keywords: F2-isoprostane(s); Leukoaraiosis; matrix metalloproteinase 2; oxidative stress; stroke; white matter hyperintensity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Brain / pathology*
  • Brain Ischemia / blood
  • Brain Ischemia / pathology*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Matrix Metalloproteinase 2 / blood*
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Oxidative Stress
  • Stroke / blood
  • Stroke / pathology*
  • White Matter / pathology*


  • Biomarkers
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9