Stromal cell–derived factor-1 promoted angiogenesis and inflammatory cell infiltration in aneurysm walls

Laboratory investigation

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  • 1 Departments of Neurological Surgery and
  • 2 Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida
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Object

A small percentage of cerebral aneurysms rupture, but when they do, the effects are devastating. Current management of unruptured aneurysms consists of surgery, endovascular treatment, or watchful waiting. If the biology of how aneurysms grow and rupture were better known, a novel drug could be developed to prevent unruptured aneurysms from rupturing. Ruptured cerebral aneurysms are characterized by inflammation-mediated wall remodeling. The authors studied the role of stromal cell–derived factor-1 (SDF-1) in inflammation-mediated wall remodeling in cerebral aneurysms.

Methods

Human aneurysms, murine carotid artery aneurysms, and murine intracranial aneurysms were studied using immunohistochemistry. Flow cytometry analysis was performed on blood from mice developing carotid or intracranial aneurysms. The effect of SDF-1 on endothelial cells and macrophages was studied by chemotaxis cell migration assay and capillary tube formation assay. Anti–SDF-1 blocking antibody was given to mice and compared with control (vehicle)-administered mice for its effects on the walls of carotid aneurysms and the development of intracranial aneurysms.

Results

Human aneurysms, murine carotid aneurysms, and murine intracranial aneurysms all expressed SDF-1, and mice with developing carotid or intracranial aneurysms had increased progenitor cells expressing CXCR4, the receptor for SDF-1 (p < 0.01 and p < 0.001, respectively). Human aneurysms and murine carotid aneurysms had endothelial cells, macrophages, and capillaries in the walls of the aneurysms, and the presence of capillaries in the walls of human aneurysms was associated with the presence of macrophages (p = 0.01). Stromal cell–derived factor-1 promoted endothelial cell and macrophage migration (p < 0.01 for each), and promoted capillary tube formation (p < 0.001). When mice were given anti–SDF-1 blocking antibody, there was a significant reduction in endothelial cells (p < 0.05), capillaries (p < 0.05), and cell proliferation (p < 0.05) in the aneurysm wall. Mice given anti–SDF-1 blocking antibody developed significantly fewer intracranial aneurysms (33% vs 89% in mice given control immunoglobulin G, respectively; p < 0.05).

Conclusions

These data suggest SDF-1 is associated with angiogenesis and inflammatory cell migration and proliferation in the walls of aneurysms, and may have a role in the development of intracranial aneurysms.

Abbreviations used in this paper:FBS = fetal bovine serum; HUVEC = human umbilical vein endothelial cell; IgG = immunoglobulin G; SCA-1 = stem cell antigen-1; SDF-1 = stromal cell–derived factor-1; STA = superficial temporal artery; VEGF = vascular endothelial growth factor.

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Contributor Notes

Address correspondence to: Brian L. Hoh, M.D., University of Florida Department of Neurosurgery, McKnight Brain Institute, 1149 Newell Dr., Rm. L2-100, Gainesville, FL 32611. email: brian.hoh@neurosurgery.ufl.edu.

Please include this information when citing this paper: published online October 25, 2013; DOI: 10.3171/2013.9.JNS122074.

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