Abstract 109: Tumor Necrosis Factor Inducible Gene 6 Protein (TSG-6) is Highly Expressed in Human Abdominal Aortic Aneurysms

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
S. Keisin Wang ◽  
Linden Green ◽  
Jie Xie ◽  
Raghu Motaganahalli ◽  
Andres Fajardo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Aortic Wall ◽  
Mononuclear Cells ◽  
Tissue Concentration ◽  
Macrophage Polarization ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Abdominal Aortic ◽  
Anti Inflammatory

Objective: The formation of an abdominal aortic aneurysm (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 contribute to AAA progression, however have yet to be characterized robustly. Here, we describe the role of the anti-inflammatory cytokine TSG-6 (TNF-stimulated gene-6) in AAA formation. Methods: Blood and aortic tissue samples were collected from patients undergoing elective AAA screening and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Cytokine concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS analysis. 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 aorta 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 the majority of 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 in the aortic wall, however M1/M2 ratios were unchanged from healthy controls. Additionally, 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 resultant vessel breakdown. From our results, we suggest TSG-6 is elevated in the AAA patient as a compensatory anti-inflammatory feedback mechanism. However, it’s effects may be abrogated by defects in CD44, its cognate receptor or downstream signaling pathways, future areas for investigation.

scholarly journals Protective Role of C3aR (C3a Anaphylatoxin Receptor) Against Atherosclerosis in Atherosclerosis-Prone Mice

2020 ◽  
Vol 40 (9) ◽  
pp. 2070-2083
Author(s):  
Lin-Lin Wei ◽  
Ning Ma ◽  
Kun-Yi Wu ◽  
Jia-Xing Wang ◽  
Teng-Yue Diao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Protective Role ◽  
Plaque Burden ◽  
Aortic Tissue ◽  
M2 Macrophage ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Objective: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar −/− /Apoe −/− mice were generated by cross-breeding of atherosclerosis-prone Apoe −/− mice and C3ar −/− mice. C3ar −/− /Apoe −/− mice and Apoe −/− mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b + leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe −/− mice, C3ar −/− /Apoe −/− mice developed more severe atherosclerosis. In addition, C3ar −/− /Apoe −/− mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. Conclusions: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis–mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.

scholarly journals Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion through Paracrine Factors

2017 ◽  
Vol 26 (2) ◽  
pp. 173-189 ◽  
Author(s):  
Jie Xie ◽  
Thomas J. Jones ◽  
Dongni Feng ◽  
Todd G. Cook ◽  
Andrea A. Jester ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Mononuclear Cells ◽  
Aortic Tissue ◽  
M2 Macrophage ◽  
Adipose Derived Stem Cells ◽  
M2 Macrophages ◽  
Paracrine Factors ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28− T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold ( n = 5, p < 0.01), while decreasing CD4+CD28− (-28%), CD8+CD28− T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1−LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold ( n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression.

scholarly journals Is aortic aneurysm preventable?

2017 ◽  
Vol 5 (2) ◽  
pp. 72-78 ◽  
Author(s):  
Undurti N. Das
Keyword(s):  
Aortic Aneurysm ◽  
Aortic Wall ◽  
Experimental Models ◽  
Aortic Tissue ◽  
Ang Ii ◽  
Epa And Dha ◽  
Abdominal Aortic ◽  
Chronic Inflammatory Condition ◽  
Beneficial Action ◽  
Anti Inflammatory

Abstract Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition, triggered by the local accumulation of macrophages, oxidative stress and damage to the aortic wall. Pro-inflammatory eicosanoids seem to play a significant role in AAA. The pro-inflammatory events seen in AAA could be due to a deficiency of anti-inflammatory eicosanoids such as lipoxin A4 (LXA4), resolvins, protectins and maresins as a result of reduced tissue concentrations of their precursors: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Thus, an imbalance between pro- and anti-inflammatory eicosanoids may underlie AAA. Angiotensin-II (Ang-II), a pro-inflammatory molecule, seems to have a role in AAA. I propose that AAA is due to the local (abdominal aortic wall) deficiency of AA and other PUFAs and their anti-inflammatory metabolites especially LXA4. The beneficial action of EPA and DHA reported in the animal experimental models of AAA induced by Ang-II infusion can be attributed to their (EPA and DHA) ability to enhance the formation of not only resolvins, protectins and maresins but also LXA4. It is likely that abdominal aortic tissue (endothelial cells, smooth muscle cells and other cells) may be deficient in AA, EPA and DHA, and have defective activity of 5-, 12-, and 15-lipoxygenases and cyclooxygenase, especially COX-2 resulting in decreased formation of LXA4, resolvins, protectins and maresins. Thus, methods designed to enhance the formation of LXA4 and other anti-inflammatory eicosanoids may form a new approach to prevent and manage AAA.

scholarly journals WALL STRESS IN ASCENDING AORTA ANEURYSMS AS A PREDICTIVE FACTOR OF BREAKAGE

2021 ◽  
Vol 108 (Supplement_3) ◽  
Author(s):  
R J Burgos Lázaro ◽  
N Burgos Frías ◽  
S Serrano-Fiz García ◽  
V Ospina Mosquera ◽  
F Rojo Pérez ◽  
...  
Keyword(s):  
Aortic Wall ◽  
Wall Stress ◽  
Middle Layer ◽  
Ascending Aorta ◽  
Aortic Aneurysms ◽  
Maximum Diameter ◽  
Resistance Factors ◽  
Risk Of Rupture ◽  
Traction Test

Abstract INTRODUCTION The surgical indication for ascending aortic aneurysms (AAA) is established when the maximum diameter &gt; 50 mm; It responds to Laplace's Law (T wall = P × r / 2e). The aim of the study is to define wall stress in AAA. MATERIAL AND METHODS 218 ascending aortic walls have been studied: 96 from organ donors, and 122 from AAA: Marfán 58 (47.5%), bicuspid aortic valve 26 (21.4%), and atherosclerosis 38 (31.1%). The samples were studied "in vitro", according to the model Young's (relationship between stress and deformed area), by means of the mechanical traction test (Tension = Force / Area). The analysis was performed with the stress-elongation curve (d Tension / d Elongation). RESULTS The stress of the aortic wall, classified from highest to lowest according to pathology and age was: cystic necrosis of the middle layer, arteriosclerosis, age &gt; 60 years, between 35 and 59, and &lt; 34 years. The stress of “control aortas” wall increased directly in relation to the age of the donors. CONCLUSIONS The maximum diameter of the ascending aorta, the patient's type of pathology and age are factors that affect the maximum tension of the aortic wall and resistance, factors that allow differentiation and prediction of the risk of rupture of the AAA. The validation of the results obtained through numerical simulation was significant and the uniaxial analysis has modeled the response of the vessels to their internal pressure.

scholarly journals In Vitro Anti-Inflammatory and Immunomodulatory Activities of an Extract from the Roots of Bupleurum rotundifolium

Medicines ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 101 ◽  
Author(s):  
Cholet ◽  
Decombat ◽  
Vareille-Delarbre ◽  
Gainche ◽  
Berry ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Polymorphonuclear Neutrophils ◽  
Ros Production ◽  
Peripheral Blood Mononuclear ◽  
Aerial Parts ◽  
Bupleurum Scorzonerifolium Willd ◽  
Anti Inflammatory ◽  
Inflammatory Profile ◽  
Bupleurum Scorzonerifolium

Background: Some Bupleurum species, such as the Bupleurum chinense DC. or the Bupleurum scorzonerifolium Willd have been extensively studied (especially their roots) for the treatment of inflammation. In contrast, only compounds extracted from the aerial parts of Bupleurum rotundifolium have been studied and showed anti-inflammatory or antiproliferative activities. This study was conducted to investigate the antioxidant, anti-inflammatory, and immunomodulatory effects of Bupleurum rotundifolium roots. Methods: To tackle the various aspects of inflammation, we studied in vitro a methanolic extract from the roots of Bupleurum rotundifolium on peripheral blood mononuclear cells (PBMCs), polymorphonuclear neutrophils (PMNs), and the monocytic cells THP-1. Its antioxidant capacities and iron-chelating activity were assessed. The extract was tested on THP-1 differentiation, reactive oxygen species (ROS) production by leukocytes, neutrophils chemotaxis, cytokines, PGE2 production, and NF-κB activation in PBMCs. Results: The extract showed a decreased ROS production in stimulated cells. It increased PBMC chemokine secretion and up-regulated the differentiation of THP-1 monocytes into macrophage-like cells, indicating a potential interest of the extract in the resolution of acute inflammation. In addition, the analysis of cytokine production suggests that Bupleurum rotundifolium has immunomodulatory properties. Conclusions: Cytokines secretion, especially IL-1β and IL-12p70, provided us with a set of indicators suggesting that the extract might be able to drive the polarization of macrophages and lymphocytes toward a Th2 anti-inflammatory profile in excessive inflammation.

Abstract 116: Simvastatin Affects Monocyte Adhesion and Infiltrative Activity in Patients With Abdominal Aortic Aneurysms

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Kiana M Samadzadeh ◽  
Anthony Nguyen ◽  
Kevin C Chun ◽  
Eugene S Lee
Keyword(s):  
Abdominal Aortic Aneurysms ◽  
Statin Treatment ◽  
Aortic Aneurysms ◽  
Monocyte Adhesion ◽  
Abdominal Aortic ◽  
Monocyte Cell ◽  
High Concentrations ◽  
Statin Drugs ◽  
Monocyte Adherence

Purpose: The pleiotropic effects of statin drugs on reducing inflammation have been well regarded in decreasing AAA expansion. We hypothesize that increased monocyte activity plays a central role in AAA formation and expansion. This study examines whether statins can prevent monocyte cell adhesion, transmigration, and matrix metalloproteinase (MMP) and inhibitor (TIMP) concentrations in AAA patients compared to non-AAA patients. Methods: Peripheral blood was collected for monocyte and serum isolation from control (n=4) and AAA (n=8) patients. Monocyte adhesion and transmigration were assessed under untreated, statin treated, and statin + mevalonate (statin inhibitor) treated conditions in vitro. Luminex assays determined MMP and TIMP concentrations from cell culture and patient serum. Results: Untreated AAA patient monocytes showed higher levels of adhesion (p=0.05) and transmigration (p=0.04) compared to control subjects (Figure 1A & 1B). Statin treatment caused a decrease in AAA monocyte adherence to the endothelium (p=0.03) and high concentrations of mevalonate reversed statin treatment effects (p=0.04) (Figure 1A). A similar trend was noted in monocyte transmigration (Figure 1B). Higher concentrations of MMP-9 were found in AAA patient serum compared to controls (p=0.01) (Figure 1C). TIMP-4 concentration were decreased in AAA patients compared to controls (p=0.02) (Figure 1D). Conclusions: Statins reduce monocyte interaction with the endothelium in vitro, leading to decreased levels of MMP-9 and increased levels of TIMP-4, implying a possible mechanism by which statins reduce AAA expansion.

Inflation Testing as a Means of Measuring Failure Strength of Aortic Tissue

2003 ◽  
Author(s):  
Jeffrey N. Kinkaid ◽  
Steven P. Marra ◽  
Francis E. Kennedy ◽  
Mark F. Fillinger
Keyword(s):  
United States ◽  
Abdominal Aortic Aneurysms ◽  
The United States ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Failure Strength ◽  
Health Statistics ◽  
Mortality Risks ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abdominal Aortic Aneurysms (AAAs) are localized enlargements of the aorta. If untreated, AAAs will grow irreversibly until rupture occurs. Ruptured AAAs are usually fatal and are a leading cause of death in the United States, killing 15,000 per year (National Center for Health Statistics, 2001). Surgery to repair AAAs also carries mortality risks, so surgeons desire a reliable tool to evaluate the risk of rupture versus the risk of surgery.

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