Reduction of MMP-9 and MIF Levels is Associated with the Beneficail effects of cilostazol in the patients with Silent Brain Infarcts

Abstract

Silent brain infarcts (SBIs) are cerebral infarcts seen on brain computed tomography (CT) or magnetic resonance imaging (MRI) in the absence of any clinical symptoms of stroke. In a previous study, cilostazol was shown to prevent the appearance or progression of SBIs. The present study aimed to evaluate the possible mechanisms of cilostazol in its beneficial effects on patients with SBIs by serially measuring inflammation- and angiogenesisassociated biomarkers such as matrix metalloproteinase-9 (MMP-9), macrophage migration inhibitory factor(MIF), visceral fat–derived adipokine (visfatin), C-X-C motif ligand 12 (CXCL12), and vascular endothelial growth factor (VEGF). We consecutively enrolled 26 patients with SBIs. SBIs were interpreted by two neuroradiologists and two neurologists. MMP-9, MIF, visfatin, CXCL12, and VEGF were measured in fasting blood samples from these 26 patients and 10 healthy volunteers at baseline and after taking cilostazol (200 mg/day) for one week and for 3 months. Serum MMP-9 was higher in patients with SBIs than in healthy controls at baseline (p<0.05), and levels of MMP-9 and MIF decreased after taking cilostazol for 3 months (p<0.01). MMP-9 levels were also lower at 1 week in the cilostazol group (p<0.05). Cilostazol had no significant effect on the other inflammatory biomarkers such as visfatin, CXCL12 and VEGF. Cilostazol decreases the inflammatory biomarkers MMP-9 and MIF in patients with SBIs and it may contribute to its beneficial effects in these patients.