Critical Roles of Macrophages in the Formation of Intracranial Aneurysm

• Published in: Stroke (1970) 2011-01, Vol.42 (1), p.173-178
• Main Authors: KANEMATSU, Yasuhisa, KANEMATSU, Miyuki, HASHIMOTO, Tomoki, KURIHARA, Chie, TADA, Yoshiteru, TSOU, Tsung-Ling, VAN ROOIJEN, Nico, LAWTON, Michael T, YOUNG, William L, LIANG, Elena I, NUKI, Yoshitsugu
• Format: Article
• Language: English
• Subjects: Angiotensin II - adverse effects; Angiotensin II - pharmacology; Animals; Biological and medical sciences; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Disease Models, Animal; Diseases of the nervous system; Female; Humans; Intracranial Aneurysm - chemically induced; Intracranial Aneurysm - genetics; Intracranial Aneurysm - metabolism; Intracranial Aneurysm - pathology; Macrophages - metabolism; Macrophages - pathology; Male; Matrix Metalloproteinase 12 - genetics; Matrix Metalloproteinase 12 - metabolism; Medical sciences; Mice; Mice, Knockout; Neurology; Pancreatic Elastase - adverse effects; Pancreatic Elastase - pharmacology; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Vascular diseases and vascular malformations of the nervous system; Vasoconstrictor Agents - adverse effects; Vasoconstrictor Agents - pharmacology
• ISSN: 0039-2499; 1524-4628; 1524-4628
• DOI: 10.1161/strokeaha.110.590976

abnormal vascular remodeling triggered by hemodynamic stresses and inflammation is believed to be a key process in the pathophysiology of intracranial aneurysms. Numerous studies have shown infiltration of inflammatory cells, especially macrophages, into intracranial aneurysmal walls in humans. Using a mouse model of intracranial aneurysms, we tested whether macrophages play critical roles in the formation of intracranial aneurysms. intracranial aneurysms were induced in adult male mice using a combination of a single injection of elastase into the cerebrospinal fluid and angiotensin II-induced hypertension. Aneurysm formation was assessed 3 weeks later. Roles of macrophages were assessed using clodronate liposome-induced macrophage depletion. In addition, the incidence of aneurysms was assessed in mice lacking monocyte chemotactic protein-1 (CCL2) and mice lacking matrix metalloproteinase-12 (macrophage elastase). intracranial aneurysms in this model showed leukocyte infiltration into the aneurysmal wall, the majority of the leukocytes being macrophages. Mice with macrophage depletion had a significantly reduced incidence of aneurysms compared with control mice (1 of 10 versus 6 of 10; P