White matter hyperintensity volume correlates with matrix metalloproteinase-2 in acute ischemic stroke.
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.
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
Zachary A
ZA
Corbin
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts. Electronic address: nrost@partners.org.
Natalia S
NS
Rost
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
Svetlana
S
Lorenzano
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Walter N
WN
Kernan
Department of Health Evidence and Policy, Mt Sinai School of Medicine, New York, New York.
Michael K
MK
Parides
Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts.
Jeffrey B
JB
Blumberg
Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts.
Paul E
PE
Milbury
Neuroprotection Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts.
Ken
K
Arai
Neuroprotection Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts.
Sophia N
SN
Hartdegen
Neuroprotection Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts.
Eng H
EH
Lo
Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
Steven K
SK
Feske
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts; Department of Neurology, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
Karen L
KL
Furie
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000097:blood / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D020521:Stroke / Q000097:blood / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
F2-isoprostane(s); Leukoaraiosis; matrix metalloproteinase 2; oxidative stress; stroke; white matter hyperintensity