Syndecan-1 displays a protective role in aortic aneurysm formation by modulating T cell-mediated responses.
Arterioscler Thromb Vasc Biol
; 32(2): 386-96, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-22173227
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. METHODS ANDRESULTS:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
/
Aneurisma da Aorta Abdominal
/
Sindecana-1
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article