Abstract 5193: Syndecan-1 is Protective in Atherosclerosis
Background: Syndecan-1 is a cell surface heparan sulfate proteoglycan characterized by highly regulated expression during development, neoplasia, and wound repair. The biological function of syndecan-1 is primarily exerted via pendant glycosaminoglycans that sequester and regulate the activity of heparin-binding growth factors and chemokines. Several studies have documented a protective role for syndecan-1 in inflammatory disease; however, the functional role syndecan-1 in atherosclerotic lesion formation has not been previously investigated.
Methods: Standard cross-breeding was used to generate ApoE−/−Sdc-1−/− double knockout mice which were maintained on a Western diet for 8 weeks to induce atherosclerotic lesion formation, results were compared to ApoE−/− Sdc-1+/+mice (n=19 each group). Brachiocephalic lesion area was quantified in 3 consecutive (hematoxylin and eosin stained) tissue sections with a 50 μm interval distance. Standard immunohistochemistry was used to characterize both murine and human atherosclerotic tissue samples. Serum was collected at 8 weeks via cardiac puncture, circulating levels of syndecan-1 were analyzed using slot blot analysis with mAb against mouse syndecan-1 (281–1).
Results: A significant increase in atherosclerotic lesion area was measured in ApoE−/−Sdc-1−/−mice verses ApoE−/−Sdc-1+/+(88.03±8.66 vs. 57.40±8.08, P < 0.05). Atherogenic animals expressed syndecan-1 positive macrophages in early lesions and advanced lipid cores, correlative staining with human carotid plaques revealed infiltration of syndecan-1 positive macrophages in all specimens. Serum syndecan-1 was undetectable in native mouse serum, soluble syndecan-1 was observed in all mice after 8 week enrollment on the Western diet.
Conclusions: The expression of syndecan-1 is significantly increased in the vascular wall of atherogenic mice and is present in human carotid plaque specimens. ApoE−/−Sdc-1+/+displayed a significant decrease in lesion area verses ApoE−/−Sdc-1−/− mice, syndecan-1 may be an important endogenous modulator of vascular inflammation.