MMP-9, Vertebrobasilar Ectasia and Vertebral Artery Dominance in Vertigo or Dizziness Patients With Vascular Risk Factors

Abstract

Background and Purpose: Although vertebrobasilar ectasia (VBE) is diagnosed with increasing frequency, it is not clear whether this is because of altered hemodynamics caused by the effects of matrix metalloproteinases (MMPs) and/or vertebral artery dominance (VAD). Therefore, we investigate the relationship between plasma levels of MMPs and VBE in patients with vertigo or dizziness who also have vascular risk factors, in order to determine whether high levels of MMPs in VBE are independent of VAD. Methods: We prospectively studied 285 patients with vertigo or dizziness and at least one vascular risk factor. Plasma levels of MMPs, tissue inhibitor of metalloproteinases (TIMPs) and cathepsin L were measured. Subjects were classified as VBE-negative or VBE-positive, who were further classified based on the presence of VAD with magnetic resonance angiography. Acute ischemic stroke was screened by diffusion-weighted imaging, generally after bedside evaluation and the drawing of blood samples. Receiver operating characteristic (ROC) curves were applied to evaluate the utility of these potential biomarkers in predicting risk for ischemic stroke. Results: The prevalence of VBE in patients with vertigo or dizziness was 16.5%. Of the 82 patients with ischemic stroke, 14 strokes involved the cortex or subcortex. MMP-9 levels were significantly higher in the VBE-positive group than in the VBE-negative group (P = 0.022). There was a significant difference in the risk of posterior circulation ischemic stroke between the VBE-positive group and the VBE-negative group (P = 0.002). Levels of MMP-2 and cathepsin L tended to be higher in the VBE-negative group (P = 0.054, P = 0.060, respectively). Compared with the non-VAD subgroup, levels of MMP-2,−3,−9, TIMP-1,−2, and cathepsin L were similar in the VAD subgroup. ROC analysis showed that MMP-9 predicted risk for ischemic stroke (AUC = 0.582, 95%CI, 0.510-0.654, P = 0.030). Zhang et al. MMP-9 Is Associated With Vertebrobasilar Ectasia Conclusions: MMP-9 was associated with VBE and independent of VAD. High levels of MMP-9 may predict risk for ischemic stroke in patients with vertigo or dizziness who also have vascular risk factors.

Melittin-loaded Iron Oxide Nanoparticles Prevent Intracranial Arterial Dolichoectasia Development through Inhibition of Macrophage-mediated Inflammation

“…The immunohistochemistry in this study showed highly expressed MMP-9 in the arterial wall of mouse IADE, which was consistent with findings of RT-PCR. The MMP-9 expression in murine model was in line with the increased serum level of MMP-9 in patients with dolichoectasia 53 , 54 . The clinical series of vertigo patients revealed that high plasma levels of MMP-9 are associated with vertebrobasilar dolichoectasia 53 .…”

“…The MMP-9 expression in murine model was in line with the increased serum level of MMP-9 in patients with dolichoectasia 53 , 54 . The clinical series of vertigo patients revealed that high plasma levels of MMP-9 are associated with vertebrobasilar dolichoectasia 53 . MMP-9 are also elevated in arterial walls of other vascular diseases with inflammatory processes 55 - 61 .…”

“…Clinical studies showed elevated serum levels of MMP-9 in the patients who had AAA [57,58], arterial dissection [55,56], and/or intracranial aneurysm [59][60][61]. The coexistence of IADE either with saccular intracranial aneurysm or AAA is relatively common, which may suggest the wide spectrum of MMP-related disease entity [51][52][53][54][55][56][57][58][59][60][61], although it remains unclear whether the IADE and saccular aneurysm formation share a common pathogenetic mechanism. We found concomitant saccular intracranial aneurysm formation in approximately 10-20% of IADE mouse models similar to Zhu et al [31].…”

“…MMP is the family of proteolytic enzymes that degrade type IV collagen and elastin and mediate the vascular remodeling 52 . The macrophages and inflammatory cells secrete MMP-9 leading to ECM degradation and dolichoectasia 31 , 51 , 53 - 58 . The immunohistochemistry in this study showed highly expressed MMP-9 in the arterial wall of mouse IADE, which was consistent with findings of RT-PCR.…”

Modified Protocol for Establishment of Intracranial Arterial Dolichoectasia Model by Injection of Elastase Into Cerebellomedullary Cistern in Mice

“…However, this degrading process may thin or destroy the internal elastic lamina of arteries ( 14 ). In previous studies, we found that a high level of plasma MMP-9 was associated with basilar arteriectasia in dizziness or vertigo patients ( 15 , 16 ). Experiments on the elastase-induced IADE mouse model demonstrated that arterial wall dilation was characterized by internal elastic lamina rupture, inflammatory cell infiltration, and high expressions of MMP-2 and MMP-9 ( 10 ).…”