Critical roles of macrophages in the formation of intracranial aneurysm

Authors

Yasuhisa Kanematsu, University of California, San Francisco
Miyuki Kanematsu, University of California, San Francisco
Chie Kurihara, University of California, San Francisco
Yoshiteru Tada, University of California, San Francisco
Tsung Ling Tsou, University of California, San Francisco
Nico Van Rooijen, Vrije Universiteit Amsterdam
Michael T. Lawton, University of California, San FranciscoFollow
William L. Young, University of California, San Francisco
Elena I. Liang, University of California, San Francisco
Yoshitsugu Nuki, University of California, San Francisco
Tomoki Hashimoto, University of California, San FranciscoFollow

Document Type

Article

Abstract

Background and Purpose-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. Methods-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). Results-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<0.05). Similarly, there was a reduced incidence of aneurysms in mice lacking monocyte chemotactic protein-1 compared with the incidence of aneurysms in wild-type mice (2 of 10 versus 14 of 20, P<0.05). There was no difference in the incidence of aneurysms between mice lacking matrix metalloproteinase-12 and wild-type mice. Conclusions-These data suggest critical roles of macrophages and proper macrophage functions in the formation of intracranial aneurysms in this model. © 2010 American Heart Association, Inc.

Publication Date

1-1-2011

Publication Title

Stroke

ISSN

00392499

Volume

42

Issue

1

First Page

173

Last Page

178

PubMed ID

21106959

Digital Object Identifier (DOI)

10.1161/STROKEAHA.110.590976

Recommended Citation

Kanematsu, Yasuhisa; Kanematsu, Miyuki; Kurihara, Chie; Tada, Yoshiteru; Tsou, Tsung Ling; Van Rooijen, Nico; Lawton, Michael T.; Young, William L.; Liang, Elena I.; Nuki, Yoshitsugu; and Hashimoto, Tomoki, "Critical roles of macrophages in the formation of intracranial aneurysm" (2011). Neurosurgery. 1010.
https://scholar.barrowneuro.org/neurosurgery/1010