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Abstract
Background and PurposeTo test the hypothesis that the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may play a potential role in bridging vertebrobasilar dolichoectasia (VBD) with lacunar infarction (LI) and white matter hyperintensities (WMH).MethodsWe studied 212 patients with vertigo who underwent multimodal magnetic resonance imaging (MRI) tests for VBD, LI, and WMH identification. We investigated biomarkers of VBD with magnetic resonance angiography (MRA) via various physical characteristics of the vertebrobasilar arteries (VBAs). Similarly, LI and WMH biomarkers were extracted using T2-weighted and fluid attenuated inversion recovery (FLAIR) images. We first determined which of these neuroimaging markers were significant identifiers of VBD, LI and the different grades of WMH. We then sought to draw potential mechanistic conclusions from these MRI-derived parameters, by associating the aforementioned biomarkers with MMP and TIMP serum levels in patient blood samples using non-parametric statistical tests.ResultsMMP-9 serum level was significantly higher in vertigo patients with VBAs dilation and basilar artery (BA) elongation compared to those with healthy arterial size, and the ratio of MMP-9/TIMP-1 level were higher in those patients. TIMP-1 level was also markedly higher in vertigo patients with BA tortuosity than those without BA tortuosity. The bending length (BL) of the BA was positively correlated with TIMP-1. The length, BL, and tortuosity index of the BA, as well as serum levels of TIMP-1 were greater in patients with higher WMH grades compared to those with low WMH grades. The vertebral artery and BA diameters, and the levels of MMP-2, -3, -9, TIMP-2 and cathepsin L were similar in patients with different WMH grades.ConclusionIn vertigo patients, we found various probably associations between MMP-9 and TIMP-1 with arterial alterations linked to both VBD and WMH that may help with the diagnosis and treatment of such diseases in the future.
Highlights
Vertebrobasilar dolichoectasia (VBD) is a clinical dysfunction characterized by an elongated, dilated and/or tortuous vertebral artery (VA) and/or basilar artery (BA) (Gutierrez et al, 2011; Yuan et al, 2014; Zhai et al, 2018)
We found that the bending length (BL) of the BA was positively correlated with tissue inhibitor of metalloproteinases (TIMPs)-1 serum level (Figure 5) (r = 0.161, P = 0.020) though the diameter, basilar artery length (BAL) and tortuosity index (TI) of the BA were not correlated with any matrix metalloproteinases (MMPs) or TIMP serum level
We found that MMP-9 serum level was higher in vertigo patients with VBA dilation and BA elongation, and the ratio of MMP9/TIMP-1 level were higher in those patients, while TIMP-1 serum level was higher in those patients with BA tortuosity
Summary
Vertebrobasilar dolichoectasia (VBD) is a clinical dysfunction characterized by an elongated, dilated and/or tortuous vertebral artery (VA) and/or basilar artery (BA) (Gutierrez et al, 2011; Yuan et al, 2014; Zhai et al, 2018). While behavioral indicators may not be a reliable source of detecting VBD or CSVD, recent advances in magnetic resonance imaging (MRI) technology has led to the identification of various neuroimaging markers of both disease states (Pico et al, 2015; Del Brutto et al, 2017). Anatomybased MRI scans can identify lacunar infarcts (LI), white matter hyperintensities (WMH), dilated perivascular spaces, cerebral microbleeds and brain atrophy that are all regarded as indicators of CSVD (Norrving, 2015). In the current study, we employed various cutting-edge MRI techniques to identify and classify VBD and CSVD disease states in a large patient population. To test the hypothesis that the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may play a potential role in bridging vertebrobasilar dolichoectasia (VBD) with lacunar infarction (LI) and white matter hyperintensities (WMH)
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