Alternatively Activated Macrophages Play an Important Role in Vascular Remodeling and Hemorrhaging in Patients with Brain Arteriovenous Malformation

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• 作者：Yukihiko Nakamura ; MD^* ; ^&dagger ; ; Yasuo Sugita ; MD^&dagger ; ; Shinji Nakashima ; MD^* ; ^&dagger ; ; Yousuke Okada ; MD^* ; Munetake Yoshitomi ; MD^* ; Yoshizou Kimura ; MD^&dagger ; ; Hiroaki Miyoshi ; MD^&dagger ; ; Motohiro Morioka ; MD^* ; ^{mmorioka@med.kurume-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Koichi Ohshima ; MD^&dagger ;
• 关键词：Arteriovenous malformation ; alternatively activated macrophage ; perinidal dilated capillary network ; vascular remodeling ; VEGF
• 刊名：Journal of Stroke and Cerebrovascular Diseases
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：25
• 期：3
• 页码：600-609
• 全文大小：1959 K

文摘

Angiogenic and immunoactive lesions in brain arteriovenous malformation (BAVM) contribute to hemorrhagic events and the growth of BAVMs. However, the detailed mechanism is unclear. Our objective is to clarify the relationship between hemorrhagic events of BAVM and alternatively activated macrophages in the perinidal dilated capillary network (PDCN).

Methods

We examined microsurgical specimens of BVMs (n = 29) and focused on the PDCN area. Ten autopsied brains without intracranial disease were the controls. We performed immunostaining of the inflammatory and endothelial cell markers, macrophage markers (CD163 and CD68), and vascular endothelial growth factor A (VEGF-A). We evaluated each cell's density and the vessel density in the PDCN and analyzed the relationship to hemorrhagic events of BAVM.

Results

The PDCN was involved in all the resected arteriovenous malformations, and these vessels showed a high rate of CD105 expression (72.0 ± 10.64%), indicating newly proliferating vessels. Alternatively activated macrophages were found, with a high rate (85.6%) for all macrophages (controls, 56.6%). In the hemorrhagic cases, the cell density was significantly higher than that in the nonhemorrhagic cases and controls (hemorrhagic group, 290 ± 44 cells/mm²; nonhemorrhagic group, 180 ± 59 cells/mm²; and control, 19 ± 8 cells/mm²). The cell density of alternatively activated macrophages showed a positive correlation with the vessel density of the PDCN. Double immunostaining showed that VEGF-A was secreted by alternatively activated macrophages.

Conclusion

Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM.