Syndecans are differentially expressed during the course of aortic aneurysm formation

Background: The syndecan family of cell surface proteoglycans can bind and modulate the activity of a diverse group of soluble and insoluble ligands, which have been shown to modulate events relevant to acute tissue repair and chronic injury responses. The expression of members of the syndecan family of heparan sulfate proteoglycans during the course of aortic aneurysm formation has not been previously investigated. In this investigation, the spatiotemporal expression of syndecan-1, -2, and -4 was characterized in a murine model of aneurysm formation. Methods: ApoE-deficient mice were maintained on an atherogenic diet for 8 weeks with concurrent infusion of angiotensin II (0.75 mg/kg/day SQ). The expression of syndecan-1, -2, and -4 at the site of aneurysm formation was characterized by immunohistochemical staining and colocalization determined by double fluorescent immunostaining. Correlative examination was performed on tissue specimens harvested from patients at the time of open aneurysm repair. Results: In the aortic wall of age-matched, untreated mice, syndecan-4 was localized to the smooth muscle cells of the media. However, neither syndecan-1 nor syndecan-2 could be detected. Within 1 week of initiating a high fat diet and infusion of angiotensin II, syndecan-1 was abundantly expressed in infiltrating macrophages, predominantly localized to the periadventitial aorta. The expression of macrophage-associated syndecan-1 was accentuated during the course of aneurysm formation. As the aneurysm matured, syndecan-2 was abundantly expressed within the aortic thrombus and heterogeneous syndecan-4 staining noted within the aortic media. Significantly, abundant syndecan-1 positive macrophages were observed in explanted human specimens. Conclusions: Given the established functional properties of this family heparan sulfate proteoglycans, chronically accelerated macrophage syndecan-1 shedding could generate a sustained proinflammatory, proteolytic, growth-stimulating environment. As a component of a counterbalancing reparative process, cell surface syndecan-2 may assist in TGF-beta mediated responses to limit the growth of abdominal aortic aneurysms.