Biomarkers and location of atherosclerosis: matrix metalloproteinase-2 may be related to intracranial atherosclerosis.
BACKGROUND
Various biomarkers are linked with the pathophysiology of atherosclerosis. We hypothesized that these factors may be associated with the location and burden of cerebral atherosclerosis.


METHODS
We evaluated 177 consecutive patients with chronic (>6 months) ischemic stroke: 68 with small vessel occlusion (SVO) and 109 with large-artery atherosclerosis (LAA), with the latter further sub-classified into 80 patients with intracranial atherosclerosis (ICAS) and 29 with extracranial atherosclerosis (ECAS). The number of ≥50% steno-occlusions on magnetic resonance angiography was used to assess the burden of atherosclerosis. Serum concentrations of the biomarkers (matrix metalloproteinases (MMP)-2 and -9, homocysteine, interleukin (IL)-6, tumor necrosis factor-α, C-reactive protein, adiponectin, leptin, resistin, free fatty acid, and lipoprotein(a)) and the metabolic syndrome were measured in each study subject.


RESULTS
Decreased plasma concentrations of MMP-2 (p = 0.020) and homocysteine (p = 0.038) were more closely associated with ICAS than with ECAS, whereas increased IL-6 concentrations were related to severe (≥4 steno-occlusions) atherosclerosis (p = 0.031). Multiple logistic regression analysis showed that the lowest tertile of MMP-2 was independently associated with ICAS (OR 4.84, 95% CI 1.29-18.19, p = 0.022).


CONCLUSIONS
Low MMP-2 plasma levels are associated with intracranial location of cerebral atherosclerosis, suggesting that MMP-2 may play a role in the development of ICAS.
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, South Korea.
Sang-Beom
SB
Jeon
Sail
S
Chun
Smi
S
Choi-Kwon
Hyun-Sook
HS
Chi
Hyun-Wook
HW
Nah
Sun U
SU
Kwon
Won-Ki
WK
Kim
Jong S
JS
Kim
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002536:Cerebral Arteries / Q000473:pathology*; D016009:Chi-Square Distribution; D003251:Constriction, Pathologic; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D016015:Logistic Models; D018810:Magnetic Resonance Angiography; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D011237:Predictive Value of Tests; D056910:Republic of Korea; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
D015415:Biomarkers; D018836:Inflammation Mediators; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2