Differential Interstrain Susceptibility to Vertebrobasilar Dolichoectasia in a Mouse Model

Zhang, Donghui; Xing, H; Dai, Daying; Kallmes, David F.; Kadirvel, R

doi:10.3174/ajnr.a5028

Cited by 13 publications

(18 citation statements)

References 17 publications

(21 reference statements)

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“…C57BL/6J mice had a greater susceptibility to VBD induction than SV129 mice. 71 These findings are important for identifying pivotal elements relevant to the development of VBD. In the future, linkage analysis of different strains may provide new insight into the genetic determinants of VBD susceptibility.…”

Section: Genetic Factorsmentioning

confidence: 99%

“…In the C57BL/6J mice, the researchers demonstrated arterial wall dilation and elongation characterized by internal elastic lamina disruption, muscular layer discontinuity, inflammatory cell infiltration, and high MMP expression in the media. C57BL/6J mice had a greater susceptibility to VBD induction than SV129 mice [ 71 ]. These findings are important for identifying pivotal elements relevant to the development of VBD.…”

Section: Mechanisms Underlying the Association Between Iade And Csvdmentioning

confidence: 99%

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Association between Intracranial Arterial Dolichoectasia and Cerebral Small Vessel Disease and Its Underlying Mechanisms

et al. 2020

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Intracranial arterial dolichoectasia (IADE), also known as dilatative arteriopathy of the brain vessels, refers to an increase in the length and diameter of at least one intracranial artery, and accounts for approximately 12% of all patients with stroke. However, the association of IADE with stroke is usually unclear. Cerebral small vessel disease (CSVD) is characterized by pathological changes in the small vessels. Clinically, patients with CSVD can be asymptomatic or present with stroke or cognitive decline. In the past 20 years, a series of studies have strongly promoted an understanding of the association between IADE and CSVD from clinical and pathological perspectives. It has been proposed that IADE and CSVD may be attributed to abnormal vascular remodeling driven by an abnormal matrix metalloproteinase/tissue inhibitor of metalloproteinase pathway. Also, IADErelated hemodynamic changes may result in initiation or progression of CSVD. Additionally, genetic factors are implicated in the pathogenesis of IADE and CSVD. Patients with Fabry’s disease and late-onset Pompe’s disease are prone to developing concomitant IADE and CSVD, and patients with collagen IV alpha 1 or 2 gene (<i>COL4A1/COL4A2</i>) and forkhead box C1 (<i>FOXC1</i>) variants present with IADE and CSVD. Race, strain, familial status, and vascular risk factors may be involved in the pathogenesis of IADE and CSVD. As well, experiments in mice have pointed to genetic strain as a predisposing factor for IADE and CSVD. However, there have been few direct genetic studies aimed towards determining the association between IADE and CSVD. In the future, more clinical and basic research studies are needed to elucidate the causal relationship between IADE and CSVD and the related molecular and genetic mechanisms.

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Section: Genetic Factorsmentioning

confidence: 99%

Section: Mechanisms Underlying the Association Between Iade And Csvdmentioning

confidence: 99%

Association between Intracranial Arterial Dolichoectasia and Cerebral Small Vessel Disease and Its Underlying Mechanisms

et al. 2020

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“…A prospective study demonstrated that MMP-2 played a role in the etiology of dolichoectasia of cervical and intracranial carotid arteries (11). A mouse model study showed that dolichoectasia was associated with high levels of MMP-2 and MMP-9 (12). A clinical study demonstrated that dolichoectasia was associated with lower plasma levels of MMP-3 (13).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…In particular, VBD has been reported to be associated with elevated levels of MMP-9 expression alone or combined with low levels of TIMP-2 expression among individuals with HIV infection (Gutierrez et al, 2016). In a study using a mouse model focusing on differential inter-strain susceptibility to VBD, dolichoectasia was also reported to be associated with high MMP-12 and MMP-9 (Zhu et al, 2017). On the contrary, in a prospective cohort study of stroke patients, dolichoectasia was reported to be connected to a lower plasma level of MMP-3 (Pico et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Basilar Artery Tortuosity Is Associated With White Matter Hyperintensities by TIMP-1

et al. 2019

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Background and Purpose 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). Methods We 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. Results MMP-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. Conclusion In 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.

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Differential Interstrain Susceptibility to Vertebrobasilar Dolichoectasia in a Mouse Model

Abstract: C57BL/6J mice demonstrated greater susceptibility to vertebrobasilar dolichoectasia induction than SV129 mice.

Cited by 13 publications

References 17 publications

Association between Intracranial Arterial Dolichoectasia and Cerebral Small Vessel Disease and Its Underlying Mechanisms

Association between Intracranial Arterial Dolichoectasia and Cerebral Small Vessel Disease and Its Underlying Mechanisms

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

Basilar Artery Tortuosity Is Associated With White Matter Hyperintensities by TIMP-1

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