Syndecan-1 Displays a Protective Role in Aortic Aneurysm Formation by Modulating T Cell–Mediated Responses
Autor: | Pyong Woo Park, Carolyn A. Haller, Julianty Angsana, Sumona Smith, Jing Wen, Elliot L. Chaikof, Mandy L. Ford, Jiantao Xiao |
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Rok vydání: | 2012 |
Předmět: |
CD4-Positive T-Lymphocytes
Male Pathology medicine.medical_specialty T cell Inflammation Article Syndecan 1 Mice Aortic aneurysm Apolipoproteins E medicine Animals Bone Marrow Transplantation Mice Knockout biology Angiotensin II Macrophages Elastase medicine.disease Abdominal aortic aneurysm Mice Inbred C57BL medicine.anatomical_structure Models Animal Immunology biology.protein Syndecan-1 Chemokines medicine.symptom Cardiology and Cardiovascular Medicine Elastin Aortic Aneurysm Abdominal |
Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 32:386-396 |
ISSN: | 1524-4636 1079-5642 |
Popis: | 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. Conclusion— 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. |
Databáze: | OpenAIRE |
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