Role of matrix metalloproteinases in the pathogenesis of intracranial aneurysms

Zhang, Xiaoran; Ares, William J.; Taussky, Philipp; Ducruet, Andrew F; Grandhi, Ramesh

doi:10.3171/2019.4.focus19214

Cited by 50 publications

(34 citation statements)

References 65 publications

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“…The proteolytic role of MMPs in expansion of trophoblasts and cancer cells is well described 73,74 . Among the MMP superfamily, MMP‐2 and MMP‐9 are essential for the fragmentation of the internal elastic lamina in both clinical and experimental model studies 75–77 . In the present case, we could demonstrate the expression of MMP‐2 in infiltrative myxoma cells.…”

Section: Discussionsupporting

confidence: 60%

“…73,74 Among the MMP superfamily, MMP-2 and MMP-9 are essential for the fragmentation of the internal elastic lamina in both clinical and experimental model studies. [75][76][77] In the present case, we could demonstrate the expression of MMP-2 in infiltrative myxoma cells. This finding might suggest that MMP-2 play a more sustainable role in brain parenchymal seeding of myxoma cells than MMP-9.…”

Section: Discussionmentioning

confidence: 62%

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Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin‐6 and matrix metalloproteinases

et al. 2020

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Systemic embolization has been reported in up to 40% of patients with left atrial myxoma, half of them with cerebral involvement. However, development of intracerebral embolization associated with parenchymal seeding of the myxoma emboli is an extremely rare complication, with only 36 histologically diagnosed cases reported in the published literature. We describe a 69-year-old woman who arrived at the emergency service with hemiparesis associated with drug-resistant epilepsy and a medical history of resection of a left atrial myxoma 10 months previously. Cranial computed tomography revealed multiple large lesions of heterogeneous density and cystic components in the occipital lobes and posterior fossa parenchyma. Histopathological analyses after stereotactic biopsy of the occipital lesion revealed infiltrative myxoma cells with benign histological findings and uniform expression of calretinin similar to that of the primary cardiac myxoma. Additional immunohistochemical studies confirmed brain parenchymal seeding of the myxoma cells with strong expression of interleukin-6 (IL-6) and focal expression of matrix metalloproteinases-2 (MMP-2). Here, we discuss the clinicopathological features of intracerebral embolization of left atrial myxomas associated with progressive parenchymal seeding of the tumor emboli and the potential pathogenic role of IL-6 and MMPs.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 62%

Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin‐6 and matrix metalloproteinases

et al. 2020

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“…The overexpression of MMP-2 and MMP-9 in CA-induced rats reinforced the effect of CA induction with elastase treatment relative to PCA groups. These overexpressions of MMPs that are involved in the progression of CA concur with results of other studies [ 46 , 47 , 48 ]. We investigated the role that the pro-inflammatory cytokine, TNF-α, plays in the development of intracranial aneurysm.…”

Section: Discussionsupporting

confidence: 92%

Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats

et al. 2021

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Our current research aims to examine whether protocatechuic acid (PCA) can be used as a therapeutic agent for the development of cerebral aneurysm (CA) and to elucidate the mechanisms behind this. We assessed the effects of PCA at 50 and 100 mg/kg on the activation of signaling pathways for tissue necrosis factor (TNF)-α/nuclear factor (NF)-κB/nuclear factor erythroid 2 (Nrf-2) on progression and development in an elastase-induced CA model, accompanied by a high-salt diet to induce hypertension. The expression of inflammatory cytokines, chemokines, tumor necrosis factor-α, interleukins (IL)-8, IL-17, IL-6, IL-1β, and matrix metalloproteinase (MMP)-2 and MMP-9 was analyzed by ELISA, western blot, and reverse transcriptase quantative polymerase chain reaction. The expression levels of antioxidant enzymes and translocation of Nrf-2 were also determined. The group treated with PCA demonstrated a significant (P < 0.05) decrease in the aneurysmal size in rats compared to the CA-induced group. We found that PCA treatment suppressed the invasion of macrophage and activation of TNF-α/NF-κB/Nrf-2 signaling pathways. There was a significant decrease (P < 0.05) in pro-inflammatory cytokine and chemokine levels in a dose-dependent manner. We found that PCA treatment exerts protective effects by suppressing the development and progression of CA through the inhibition of inflammatory responses in macrophages via TNF-α/NF-κB/Nrf-2 signaling pathways, thus demonstrating that PCA can act as a treatment for CA.

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“…However the present study found stronger expression of vascular remodeling factor VEGF in patients with direct attachment of pituitary adenomas and cerebral aneurysms. Aneurysm formation is thought to be a result of complex interactions between biochemical and mechanical forces, and various vascular remodeling factors have been considered as causative of cerebral aneurysms and used in experimental aneurysm formation [12][13][14][15][16][17]. The present study may indicate possible VEGF-induced remodeling of the arterial walls.…”

Section: Discussionmentioning

confidence: 68%

Pituitary Adenomas Associated with Intracranial Aneurysms – The Clinical Characteristics, Therapeutic Strategies, and Possible Effects of Vascular Remodeling Factors

Ogawa¹,

Watanabe²,

Tominaga³

2020

Preprint

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Objective: Pituitary adenoma coexists with intracranial aneurysms in 2.3% to 3.6%, and intracranial aneurysms is thought to be incidental. On the other hand higher age and cavernous sinus invasion are reported to increase the coexistence rate, so these two diseases may be related. Ten males and 14 females with coexistence of pituitary adenomas and intracranial aneurysms were retrospectively investigated among 923 patients (2.6%). Patients were subdivided into two groups with/without direct attachment of cerebral aneurysms to the pituitary adenomas. The clinical characteristics, therapeutic strategies, and possible effects of vascular remodeling factors were investigated.Results: Twelve patients had functioning pituitary adenomas, and cavernous sinus invasion was identified in 7 of 24 patients. Five of these 7 patients were treated with priority for the cerebral aneurysms until 2007, whereas 14 of 17 patients without involvement of the aneurysm tip in the tumor were treated with priority for pituitary adenomas in the later period. Among vascular remodeling factors strong expression of vascular endothelial growth factor (VEGF) was significantly associated with coexistence of pituitary adenoma and cerebral aneurysm (p < 0.05). So VEGF-induced arterial wall remodeling may be part of the mechanism of association between pituitary adenomas and cerebral aneurysms, suggesting possible causative mechanism.

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Role of matrix metalloproteinases in the pathogenesis of intracranial aneurysms

Cited by 50 publications

References 65 publications

Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin‐6 and matrix metalloproteinases

Cerebral embolization associated with parenchymal seeding of the left atrial myxoma: Potential role of interleukin‐6 and matrix metalloproteinases

Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats

Pituitary Adenomas Associated with Intracranial Aneurysms – The Clinical Characteristics, Therapeutic Strategies, and Possible Effects of Vascular Remodeling Factors

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