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Published on: November 23, 2017
Macrophage migration inhibitory factor reduces apoptosis in cerebral arteriovenous malformations
Guangzhong Chen1, Meng Zheng, Hang Shu
1Department of Neurosurgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China. chengz5413@126.com
Purpose:
To investigate the expression of macrophage migration inhibitory factor (MIF) in human brain arteriovenous malformations (AVM).
Materials And Methods:
Twelve AVM specimens were obtained from patients who did not received preoperative embolization. MIF levels were measured by Western blot and matrix metalloproteinase 9 (MMP9) levels were measured by reverse transcription PCR. The expression of MIF in brain AVMs was also evaluated by immunohistochemistry and was correlated with apoptosis and the expression of cleaved caspase-3 and MMP9.
Results:
The expression of MIF, MMP9, and cleaved caspase-3 was elevated in brain AVM vessels. High levels of MIF were primarily found in the endothelium and adventitia, whereas apoptotic cells were concentrated in the smooth muscle layer.
Conclusions:
Abnormal apoptosis may be involved in the pathogenesis of brain AVM. In addition, increased MIF expression could play an important role regulating the homeostasis of AVM vessels.
Insights
Macrophage migration inhibitory factor (MIF) and MMP9 are elevated in brain arteriovenous malformations (AVM). Increased MIF expression may regulate AVM vessel homeostasis, with abnormal apoptosis potentially involved in pathogenesis.
Area of Science:
- Neuroscience
- Vascular Biology
- Pathology
Background:
- Brain arteriovenous malformations (AVMs) are complex vascular lesions.
- The molecular mechanisms underlying AVM pathogenesis remain incompletely understood.
- Macrophage migration inhibitory factor (MIF) is a key inflammatory cytokine with diverse biological roles.
Purpose of the Study:
- To investigate the expression and localization of macrophage migration inhibitory factor (MIF) in human brain arteriovenous malformations (AVMs).
- To explore the relationship between MIF, matrix metalloproteinase 9 (MMP9), cleaved caspase-3, and apoptosis in brain AVMs.
Main Methods:
- Western blot analysis was used to quantify MIF levels in twelve human brain AVM specimens.
- Reverse transcription PCR was employed to measure matrix metalloproteinase 9 (MMP9) expression.
- Immunohistochemistry was performed to evaluate MIF expression and its correlation with apoptosis and cleaved caspase-3.
Main Results:
- Elevated expression of MIF, MMP9, and cleaved caspase-3 was observed in brain AVM vessels.
- High MIF levels were predominantly detected in the endothelium and adventitia of AVMs.
- Apoptotic cells were primarily localized within the smooth muscle layer of the AVMs.
Conclusions:
- Abnormal apoptosis is implicated in the pathogenesis of brain AVMs.
- Increased MIF expression may play a crucial role in maintaining the homeostasis of AVM vessels.
- These findings suggest potential therapeutic targets for managing brain AVMs.
