Syndecan-1 May Inhibit Growth of AAAs

Newswise — Researchers from Emory University in Atlanta have determined that syndecan-1 acts as a negative regulator of proteolytic responses in the aortic wall during the formation of abdominal aortic aneurysms (AAAs) and that modulating syndecan-1 expression could provide a useful strategy for limiting aneurysm growth. Their findings will be presented during the Vascular Annual Meeting, June 5-8, in San Diego, Calif. Syndecan-1 is a member of a family of cell surface heparan sulfate proteoglycans that modulate inflammatory and growth-stimulating events relevant to acute tissue repair and chronic injury responses. The researchers have previously demonstrated that macrophage-associated syndecan-1 is expressed during the course of AAA formation in human tissue and in a murine model of angiotensin II induced aneurysm formation. The current study investigated the role of syndecan-1 in a murine model of elastase-induced AAA.

According to Elliot L. Chaikof, MD, chief of vascular surgery, 43 adult male C57BL/6 wild-type and 35 syndecan-1 knockout mice underwent transient elastase perfusion of the abdominal aorta to induce AAA. Aortic diameter was measured preperfusion, postperfusion and at harvest on 1, 4, 7 and 14 days. Aortas from each group and each time point were analyzed for inflammatory response by immunohistochemical staining and matrix metalloproteinase-2 (MMP-2) and MMP-9 activity by gelatin zymography. Macrophages were harvested four days after injection of 1 mL of 1 percent thioglycollate into the peritoneal cavity of wild-type or syndecan-1 knockout mice. Conditioned media were collected, samples normalized by initial cell count and total protein assay, and proteolytic activity was measured using elastin and collagen substrates.

All mice developed AAA at day 14, but syndecan-1 knockout mice displayed a significantly greater extent of dilatation than wild-type mice (1.51±0.14 mm vs. 1.29±0.06 mm). Histological analysis revealed robust expression of Syndecan-1 at the site AAA formation in wild-type mice. Gelatin zymography demonstrated significantly greater levels of MMP-2 and MMP-9 activity in syndecan-1 knockout mice at 7 days (proMMP-9: 0.816±0.125 vs. 0.602±0.090; p=0.0069; proMMP-2: 0.506±0.081 vs. 0.206±0.037). A significantly higher level of proteolytic activity was observed in media obtained from knockout macrophages than from wild type controls.

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