title: Syndecan-1 displays a protective role in aortic aneurysm formation by modulating T cell-mediated responses.
abstract: 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.
  
  
  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.
authors.affiliation: BIDMC, 110 Francis St, Suite 9F, Boston, MA 02215 or Carolyn A. Haller, PhD, BIDMC, 110 Francis St, Suite 9F, Boston, MA 02215, USA.
authors.forename: Jiantao
authors.initials: J
authors.lastname: Xiao
authors.forename: Julianty
authors.initials: J
authors.lastname: Angsana
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.forename: Sumona V
authors.initials: SV
authors.lastname: Smith
authors.forename: Pyong Woo
authors.initials: PW
authors.lastname: Park
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ford
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Haller
authors.forename: Elliot L
authors.initials: EL
authors.lastname: Chaikof
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D018925:Chemokines / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D053668:Syndecan-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D018925:Chemokines; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D000804:Angiotensin II