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

• Published in: Journal of stroke and cerebrovascular diseases Vol. 25; no. 3; pp. 600 - 609
• Main Authors: Nakamura, Yukihiko, MD, Sugita, Yasuo, MD, Nakashima, Shinji, MD, Okada, Yousuke, MD, Yoshitomi, Munetake, MD, Kimura, Yoshizou, MD, Miyoshi, Hiroaki, MD, Morioka, Motohiro, MD, Ohshima, Koichi, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2016
• Subjects: Adolescent; Adult; alternatively activated macrophage; Antigens, CD - metabolism; Arteriovenous malformation; Cardiovascular; Cell Count; Child; Female; Hemorrhage - etiology; Humans; Intracranial Arteriovenous Malformations - pathology; Intracranial Arteriovenous Malformations - physiopathology; Macrophages - pathology; Male; Middle Aged; Neurology; Neutrophils - metabolism; Neutrophils - pathology; perinidal dilated capillary network; Retrospective Studies; Vascular Endothelial Growth Factor A - metabolism; vascular remodeling; Vascular Remodeling - physiology; VEGF; Young Adult; perinidal dilated capillary network; vascular remodeling; VEGF; Arteriovenous malformation; alternatively activated macrophage
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2015.11.034

Background 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.