TSG-6 is highly expressed in human abdominal aortic aneurysms

Abstract

Background The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of pro-inflammatory forces that result in smooth muscle cell apoptosis, extra-cellular matrix degradation, and progressive diameter expansion. Additional defects in the anti-inflammatory response may also play a role, but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent anti-inflammatory protein involved in extracellular matrix stabilization and cell migration active in many pathological conditions. Here, we describe its role in AAA formation. Methods Blood and/or aortic tissue samples were collected from organ donors, subjects undergoing elective AAA screening, and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Protein concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS. In vitro, macrophage polarization from monocytes were performed with young, healthy donor PBMCs. Results TSG-6 was found to be abnormally elevated in both the plasma and aortic wall of patients with AAA compared to healthy and risk-factor matched non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less diseased proximal and distal shoulders compared to the central aspect of the aneurysm. IHC localized most TSG-6 to the tunica media with minor expression in the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2 macrophages where also observed, however M1/M2 ratios were unchanged from healthy controls. We observed no difference in M1/M2 ratios in the peripheral blood of risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the polarization of the anti-inflammatory M2 phenotype in vitro. Conclusions AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation.

Adipose-Derived Mesenchymal Stem Cells Promote M2 Macrophage Phenotype through Exosomes

“…However, in terms of immunosuppression, the interactive possibility of other immune cells cannot be excluded. IL-10 and TSG-6 are the main anti-inflammatory factors expressed in M2 macrophages [22]. In the present study, iM Φ exhibited the highest increase in the expression levels of IL-10 and TSG-6 as compared to those in other AdMSCs and AdMSCs plus iM Φ .…”

Diverse roles of macrophage polarization in aortic aneurysm: destruction and repair

“…Recently, new phenotypes of macrophages were described to result from additional stimuli under certain microenvironments. These include hemorrhage-associated macrophages called Mhem (induced by hemoglobin) [ 23 ], macrophages stimulated with oxidized phospholipids (Mox) [ 24 ], and M4 macrophages induced by chemokine ligand 4 [ 25 ], tumor-associated macrophages (TAMs) etc. The currently available data indicate that macrophage polarization is a multifactorial process in which a large number of factors can be involved, producing different activation scenarios (Fig.…”

Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis

“…Recent studies have shown the presence of TSG-6 expression in human coronary atherosclerotic plaques and abdominal aortic aneurysms [ 10 , 48 ]. The expression of TSG-6 is almost absent in normal and non-stenotic coronary arteries from non-CAD and CAD patients respectively [ 10 ].…”

“…In the stenotic coronary arteries from CAD patients, TSG-6 is highly expressed in the fibrous cap within atherosclerotic plaques [ 10 ]. In addition, the expression of TSG-6 is observed in the tunica media of human abdominal aortic aneurysms [ 48 ]. These findings suggest that TSG-6 is produced to counteract the progression of atherosclerotic lesions and to stabilize vulnerable plaques and aneurysms.…”