Biomarkers and location of atherosclerosis: Matrix metalloproteinase-2 may be related to intracranial atherosclerosis

BackgroundVarious biomarkers are linked with the pathophysiology of atherosclerosis. We hypothesized that these factors may be associated with the location and burden of cerebral atherosclerosis.MethodsWe 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.ResultsDecreased 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).ConclusionLow 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.

► Plasma biomarker profiles may be associated with the location of cerebral atherosclerosis in patients with chronic ischemic stroke. ► Low matrix metalloproteinase-2 plasma level was significantly associated with the intracranial cerebral atherosclerosis. ► Low level of plasma homocysteine was associated with intracranial cerebral atherosclerosis. ► Increased IL-6 concentrations were related to the burden of cerebral atherosclerosis.