TSG-6 is highly expressed in human abdominal aortic aneurysms

S. Keisin Wang, Jie Xie, Linden A. Green, Robert A. McCready, Raghu Motaganahalli, Andres Fajardo, Clifford C. Babbey, Michael Murphy

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of proinflammatory forces that result in smooth muscle cell apoptosis, extracellular matrix degradation, and progressive diameter expansion. Additional defects in the antiinflammatory response may also play a role but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent antiinflammatory 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 was 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 with 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 with 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 antiinflammatory M2 phenotype in vitro. Conclusions AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to the vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation.

Original languageEnglish (US)
Pages (from-to)311-319
Number of pages9
JournalJournal of Surgical Research
Volume220
DOIs
StatePublished - Dec 1 2017

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Abdominal Aortic Aneurysm
Genes
Anti-Inflammatory Agents
Aortic Aneurysm
Tissue Donors
Extracellular Matrix
Macrophages
Tunica Media
Adventitia
Smooth Muscle Myocytes
Cell Movement
Aneurysm
Monocytes
Proteins
Enzyme-Linked Immunosorbent Assay
Apoptosis
Phenotype
Gene Expression
Population

Keywords

  • Abdominal aortic aneurysm
  • Inflammation
  • Macrophage
  • TSG-6

ASJC Scopus subject areas

  • Surgery

Cite this

TSG-6 is highly expressed in human abdominal aortic aneurysms. / Wang, S. Keisin; Xie, Jie; Green, Linden A.; McCready, Robert A.; Motaganahalli, Raghu; Fajardo, Andres; Babbey, Clifford C.; Murphy, Michael.

In: Journal of Surgical Research, Vol. 220, 01.12.2017, p. 311-319.

Research output: Contribution to journalArticle

Wang, S. Keisin ; Xie, Jie ; Green, Linden A. ; McCready, Robert A. ; Motaganahalli, Raghu ; Fajardo, Andres ; Babbey, Clifford C. ; Murphy, Michael. / TSG-6 is highly expressed in human abdominal aortic aneurysms. In: Journal of Surgical Research. 2017 ; Vol. 220. pp. 311-319.
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abstract = "Background The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of proinflammatory forces that result in smooth muscle cell apoptosis, extracellular matrix degradation, and progressive diameter expansion. Additional defects in the antiinflammatory response may also play a role but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent antiinflammatory 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 was 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 with 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 with 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 antiinflammatory M2 phenotype in vitro. Conclusions AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to the vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation.",
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T1 - TSG-6 is highly expressed in human abdominal aortic aneurysms

AU - Wang, S. Keisin

AU - Xie, Jie

AU - Green, Linden A.

AU - McCready, Robert A.

AU - Motaganahalli, Raghu

AU - Fajardo, Andres

AU - Babbey, Clifford C.

AU - Murphy, Michael

PY - 2017/12/1

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N2 - Background The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of proinflammatory forces that result in smooth muscle cell apoptosis, extracellular matrix degradation, and progressive diameter expansion. Additional defects in the antiinflammatory response may also play a role but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent antiinflammatory 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 was 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 with 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 with 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 antiinflammatory M2 phenotype in vitro. Conclusions AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to the vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation.

AB - Background The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of proinflammatory forces that result in smooth muscle cell apoptosis, extracellular matrix degradation, and progressive diameter expansion. Additional defects in the antiinflammatory response may also play a role but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent antiinflammatory 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 was 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 with 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 with 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 antiinflammatory M2 phenotype in vitro. Conclusions AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to the vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation.

KW - Abdominal aortic aneurysm

KW - Inflammation

KW - Macrophage

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