Syndecan-1 modulates the motility and resolution responses of macrophages.

OBJECTIVE: Syndecan-1 (Sdc-1) is a member of a family of cell surface proteoglycans, which has been reported to participate in the regulation of events relevant to tissue repair and chronic injury responses, including cell-substrate interactions, matrix remodeling, and cell migration. In this study, we report the functional significance of Sdc-1 in polarized macrophage populations and its role in adhesion and motility events relevant to resolution of the inflammatory program. APPROACH AND RESULTS: Macrophage Sdc-1 expression is associated with differentiated M2 macrophages with high intrinsic motility, and Sdc-1 deficiency is characterized by impaired migration and enhanced adhesion. Leukocyte infiltration and emigration were examined in a thioglycollate-induced model of peritonitis in Sdc-1(+/+) and Sdc-1(-/-) mice. Although the infiltration of inflammatory cells was similar in both cohorts, a significant delay in the lymphatic clearance of Sdc-1(-/-) macrophages was observed. Moreover, we observed enhanced inflammation and greater burden of atherosclerotic plaques in ApoE(-/-)Sdc-1(-/-) mice maintained on a Western diet. CONCLUSIONS: These results demonstrate that defective motility in Sdc-1(-/-) macrophages promotes a persistent inflammatory state with relevance to the pathogenesis of atherosclerosis.

Delayed reconstruction of the superior mesenteric vein with autogenous femoral vein.

A 38-year-old man underwent ligation of the superior mesenteric vein due to traumatic disruption. He developed severe bowel edema with large fluid losses through the open abdominal incision. On postoperative day 9, a superior mesenteric vein bypass was performed with autogenous femoral vein, and this resulted in prompt resolution of the bowel edema and allowed abdominal wound closure. He was able to resume a normal diet and was discharged on postinjury day 39. A magnetic resonance imaging scan performed 1 year later showed a patent graft.

Syndecan-1 displays a protective role in aortic aneurysm formation by modulating T cell-mediated responses.

OBJECTIVE: Chronic inflammation drives progressive and pathological remodeling inherent to formation of abdominal aortic aneurysm (AAA). Syndecan-1 (Sdc-1) is a cell surface heparan sulfate proteoglycan that displays the capacity to modulate inflammatory processes within the vascular wall. In the current investigation, the role of Sdc-1 in AAA formation was examined using 2 models of experimental aneurysm induction, angiotensin II infusion and elastase perfusion. METHODS AND RESULTS: Sdc-1 deficiency exacerbated AAA formation in both experimental models and was associated with increased degradation of elastin, greater protease activity, and enhanced inflammatory cell recruitment into the aortic wall. Bone marrow transplantation studies indicated that deficiency of Sdc-1 in marrow-derived cells significantly contributed to AAA severity. Immunostaining revealed augmented Sdc-1 expression in a subset of AAA localized macrophages. We specifically characterized a higher percentage of CD4(+) T cells in Sdc-1-deficient AAA, and antibody depletion studies established the active role of T cells in aneurysmal dilatation. Finally, we confirmed the ability of Sdc-1 macrophage to modulate the inflammatory chemokine environment. CONCLUSIONS: These investigations identify cross-talk between Sdc-1-expressing macrophages and AAA-localized CD4(+) T cells, with Sdc-1 providing an important counterbalance to T-cell-driven inflammation in the vascular wall.

A single-institution experience with the AneuRx Stent Graft for endovascular repair of abdominal aortic aneurysm.

We report our experience of endovascular repair of infrarenal abdominal aortic aneurysms (EVAR) using the modular AneuRx Stent Graft System. We retrospectively reviewed the outcomes of 113 patients who underwent EVAR with the AneuRx system performed at our institution between October 1999 and August 2003. The mean age of this group was 72.5 years, with 71% (n = 80) over the age of 70 years and 95% (n = 107) males. Aneurysm diameter ranged 4.0-9.0 cm, with 33% (n = 37) >6.0 cm. The average duration of late follow-up was 32.6 +/- 24.8 months (median = 37). Successful deployment of the modular AneuRx system was noted in all patients. There were no immediate operative conversions, deaths within 24 hr of operation, or type I or III endoleaks observed at the completion of the procedure. Thirty-day mortality was 3.5% (n = 4). Acute deployment-related complications occurred in 10% (n = 13) of patients and included misdeployment, operative bleeding, arterial perforation/dissection, and access site complications. Acute systemic complications were present in nine patients, predominantly renal and cardiac complications. An endoleak noted at any time occurred in 25% of patients, with 40% of those requiring a secondary intervention. Two patients suffered late aneurysm rupture due to a type I endoleak and graft infection. Kaplan-Meier analysis revealed 5-year freedom from secondary intervention of 72.4%; freedom from aneurysm-related death of 93.9%; and probability of survival based on all-cause mortality of 60.1%. Endovascular treatment with the modular AneuRx Stent Graft System is safe and effective, producing acceptable rates of disease-free survival and mid-term clinical outcome.

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.

Conformational Study of trans-Cyclododecene by Dynamic NMR Spectroscopy and Computational Methods.

The (13)C spectrum of trans-cyclododecene (1) dissolved in propane showed seven peaks for the olefinic carbons at -164.5 degrees C, corresponding to three conformations of C(1) symmetry and a fourth conformation, with a population of 20.1%, of C(2) symmetry. The populations of the C(1) conformations were 57.0, 18.6, and 4.3%. Conformational space was searched for 1 using MM2. Free energies and populations were calculated by MM3, and the results of the low-temperature NMR study are discussed in terms of these calculations and the (13)C chemical shifts calculated for eight conformations by the GIAO method at the HF/6-311G level. The conformations of 1 and cyclododecane (2) are compared.