scholarly journals miR-195 suppresses abdominal aortic aneurysm through the TNF-α/NF-κB and VEGF/PI3K/Akt pathway

2018 ◽  
Author(s):  
Xiaohui Ma ◽  
Hairong Yao ◽  
Yuhong Yang ◽  
Long Jin ◽  
Yu Wang ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Akt Pathway ◽  
Abdominal Aortic ◽  
Tnf Α

scholarly journals Effect of Cyclic Stretch on Vascular Endothelial Cells and Abdominal Aortic Aneurysm (AAA): Role in the Inflammatory Response

2019 ◽  
Vol 20 (2) ◽  
pp. 287 ◽  
Author(s):  
Martina Ramella ◽  
Giulia Bertozzi ◽  
Luca Fusaro ◽  
Maria Talmon ◽  
Marcello Manfredi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Inflammatory Response ◽  
Mechanical Stress ◽  
Mechanical Stimulation ◽  
Cyclic Stretch ◽  
Abdominal Aortic ◽  
Tnf Α

Abdominal aortic aneurysm (AAA) is a focal dilatation of the aorta, caused by both genetic and environmental factors. Although vascular endothelium plays a key role in AAA progression, the biological mechanisms underlying the mechanical stress involvement are only partially understood. In this study, we developed an in vitro model to characterize the role of mechanical stress as a potential trigger of endothelial deregulation in terms of inflammatory response bridging between endothelial cells (ECs), inflammatory cells, and matrix remodeling. In AAA patients, data revealed different degrees of calcification, inversely correlated with wall stretching and also with inflammation and extracellular matrix degradation. In order to study the role of mechanical stimulation, endothelial cell line (EA.hy926) has been cultured in healthy (10% strain) and pathological (5% strain) dynamic conditions using a bioreactor. In presence of tumor necrosis factor alpha (TNF-α), high levels of matrix metalloproteinase-9 (MMP-9) expression and inflammation are obtained, while mechanical stimulation significantly counteracts the TNF-α effects. Moreover, physiological deformation also plays a significant role in the control of the oxidative stress. Overall our findings indicate that, due to wall calcification, in AAA there is a significant change in terms of decreased wall stretching.

P732Maternal high-fat diet promotes the expansion of abdominal aortic aneurysm in adult offspring by enhancing osteoclast-like macrophage differentiation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Saburi ◽  
H Yamada ◽  
N Wada ◽  
S Motoyama ◽  
T Sugimoto ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
High Fat Diet ◽  
Fold Increase ◽  
Adult Offspring ◽  
High Fat ◽  
Double Positive ◽  
Abdominal Aortic ◽  
Tnf Α ◽  
Outer Circumference

Abstract Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation. Methods and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating and received during pregnancy and lactation. In eight-week-old offspring of both genders, AAA was induced with the application of 0.5M calcium chloride (CaCl2) on the infrarenal aorta. Male offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND) (P<0.05). The lengths of outer circumference assessed by histological analysis were increased in O-HFD (P<0.05). Likewise, female O-HFD showed a greater length of outer circumference than female O-ND (P<0.05). While the number of F4/80-positive cells at 1 wk after surgery was comparable between the male O-HFD and O-ND, the percentage of MMP-9/F4/80 double-positive cells was significantly increased in male O-HFD. Consistently, fluorescent image of abdominal aorta taken by IVIS at 1 wk after surgery revealed a 2-fold increase in MMP activity (P<0.01). Intriguingly, F4/80-positive cells in male O-HFD showed a 2.5-fold increase in co-staining with tartrate-resistant acid phosphate (TRAP), typical marker of osteoclast-like macrophages which abundantly secrete proteases than classically activated macrophages (M1), while the percentage of TNF-α/F4/80 double-positive cells was comparable between the 2 groups. Pharmacological inhibition of osteoclastogenesis by zoledronic acid (ZA) (100μg/kg) completely abolished the exaggerated AAA development in male O-HFD to a similar extent of that in male O-ND, while AAA development in male O-ND mice did not change even after ZA treatment. Furthermore, in vitro TNF-α-induced osteoclast differentiation of bone marrow-derived macrophages (BMDMs) showed a significantly higher number of TRAP-positive cells, accompanied by increased calcitonin receptor mRNA expression. Western blotting analysis showed that protein expression level of NFATc1, master regulator of osteoclastogenesis, was significantly higher in BMDM of O-HFD than O-ND. Conclusion Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development.

Maternal high-fat diet promotes the expansion of abdominal aortic aneurysm in adult offspring by enhancing osteoclast-like macrophage differentiation through down-regulation of IRF8 expression

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Saburi ◽  
H Yamada ◽  
T Sugimoto ◽  
H Kubota ◽  
D Miyawaki ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
High Fat Diet ◽  
Fold Increase ◽  
Adult Offspring ◽  
High Fat ◽  
Double Positive ◽  
Abdominal Aortic ◽  
Tnf Α ◽  
Outer Circumference

Abstract Background and objective Maternal high-fat diet (HFD) has been shown to modulate vascular function and remodeling in adult offspring. Here, we investigated the impact of maternal HFD on abdominal aortic aneurysm (AAA) formation. Methods and results Eight-week-old female wild-type mice (C57BL/6) were fed a HFD or normal diet (ND) one week prior to mating, and the diet was continued throughout gestation and lactation. In eight-week-old male offspring, AAA was induced with the application of 0.5 M calcium chloride (CaCl2) on the infrarenal aorta. Offspring of HFD-fed dams (O-HFD) showed a significant increase in maximum outer diameter of AAA at 1, 4 and 8 weeks after surgery compared with offspring of ND-fed dams (O-ND). The lengths of outer circumference assessed by histological analysis were increased in O-HFD (p&lt;0.05). Likewise, female O-HFD showed a greater length of outer circumference than female O-ND (p&lt;0.05). While the number of F4/80-positive cells at 1 wk after surgery was comparable in the O-HFD and O-ND, the percentage of MMP-9/F4/80 double-positive cells was significantly increased in O-HFD. Consistently, fluorescent image of abdominal aorta taken by IVIS at 1 wk after surgery revealed a 2-fold increase in MMP activity. Intriguingly, F4/80-positive cells in O-HFD showed a 2.5-fold increase in co-staining with tartrate-resistant acid phosphate (TRAP), typical marker of osteoclast-like macrophages which abundantly secrete proteases than classically activated macrophages, while the percentage of TNF-α/F4/80 double-positive cells was comparable in the two groups. Pharmacological inhibition of osteoclastogenesis by zoledronic acid (ZA) (100μg/kg) completely abolished the exaggerated AAA development in O-HFD to an extent similar to that in O-ND, while AAA development in O-ND mice did not change after ZA treatment. Furthermore, in vitro TNF-α-induced osteoclast differentiation of bone marrow-derived macrophages (BMDMs) showed a significantly higher number of TRAP-positive cells in O-HFD, accompanied by a significant increase in osteoclast-related genes expression. Western blotting analysis revealed that the expression of NFATc1, master regulator of osteoclastogenesis, was significantly higher in O-HFD than that in O-ND, and immunofluorescent imaging showed that nuclear translocation of NFATc1 upon TNF-α stimulation was significantly enhanced in O-HFD. We further examined the expression of IFN regulatory factor 8 (IRF8) which suppresses osteoclastogenesis by inhibiting the function and expression of NFATc1. IRF8 mRNA and nuclear protein expression levels were significantly lower in O-HFD than those in O-ND. Conclusion Our findings demonstrate that maternal HFD accelerates CaCl2-induced AAA expansion, accompanied by the exaggerated accumulation of osteoclast-like macrophages and augmented activity of MMPs. Inhibition of macrophages skewing toward osteoclast-like cells could be a potential therapeutic target for preventing AAA development. Funding Acknowledgement Type of funding source: None

Abstract 256: Decreased Serum MiR-155 Expression is Associated with Increased Tumor Necrosis Factor-Alpha Levels in Patients with Abdominal Aortic Aneurysm

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Arash M Afkhami ◽  
Anthony T Nguyen ◽  
Kiana M Samadzadeh ◽  
Anjelica Rona ◽  
Kevin C Chun ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Tumor Necrosis Factor ◽  
Aortic Aneurysm ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Abdominal Aortic ◽  
Tnf Α ◽  
Factor Alpha ◽  
The Relationship ◽  
Necrosis Factor

Introduction: The inflammatory response plays a crucial role in abdominal aortic aneurysm (AAA) pathogenesis and expansion. The cytokine tumor necrosis factor-alpha (TNF-α) and MicroRNA-155 (miR-155) are implicated in inflammatory diseases. Previous studies have found miR-155 regulates TNF-α expression in cardiovascular disease. However, the relationship between TNF-α expression and miR-155 in AAA disease is not fully understood. This study examines the relationship between serum TNF-α levels and miR-155 expression in AAA patients. Methods: MicroRNA’s were isolated from patient serum and quantified using Agilent BioAnalyzer 2100. MiR-155 levels were assessed using qPCR with Exiqon LNA primers and normalized using the 2-ΔΔCT method. Media was collected from the co-culture of control or AAA monocytes with endothelial cells. The supernatant was analyzed for the presence of TNF-α via Luminex ® 200 TM analyzer. AAA is defined as ≥3.0 cm in maximum aortic diameter and measurement was obtained from abdominal ultrasound. Student’s t-test was used to compare AAA and control groups for statistical analysis. Results: Average aortic diameter for AAA group was 5.1±0.7 cm and 2.4±0.4 cm for controls. Q-PCR results showed miR-155 was significantly down-regulated in serum (p=0.03) in AAA subjects (n=5) versus non-AAA controls (n=4) (Figure 1A). Serum TNF-α levels from Luminex assays trended towards greater levels in AAA patients (n=4) vs. controls (n=3) (920.1±591.1 vs. 294.8±102.2 pg/mL, p=0.14) (Figure 1B). Conclusion: Patients with AAA may have more unregulated TNF-α activity due to decreased miR-155 expression compared to controls. Serum miR-155 may serve as a potential biomarker for patients at risk for aortic expansion leading to AAA disease.

Polymorphisms in the IL-6 and TNF-α gene are associated with an increased risk of abdominal aortic aneurysm

2021 ◽  
Author(s):  
Agnieszka Jabłońska ◽  
Branislav Zagrapan ◽  
Christoph Neumayer ◽  
Wolf Eilenberg ◽  
Andreas Scheuba ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Abdominal Aortic ◽  
Increased Risk ◽  
Tnf Α

scholarly journals Effect of anti-CIRP antibody on inflammatory response, tumor formation and abdominal aortic aneurysm in rats

2020 ◽  
Vol 19 (6) ◽  
pp. 1215-1219
Author(s):  
Yuqing Wang ◽  
Lantao Lu ◽  
Weiyan Li ◽  
Shuntong Gu
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Inflammatory Reaction ◽  
Rna Binding ◽  
Tumor Formation ◽  
Maximum Diameter ◽  
Sham Operation ◽  
Abdominal Aortic ◽  
Tnf Α ◽  
Model Control

Purpose: To investigate the effect of anti-cold induced RNA binding protein (CIRP) antibody on inflammation, tumor formation and abdominal aortic aneurysm in rats.Methods: Thirty healthy male Wistar rats were assigned to pseudo-operation, abdominal aortic aneurysm model, and anti-CIRP groups, with 10 in each group. The levels of CIRP, TNF- α, monocyte giant cytokine chemokine-1 (MCP-1), Toll-like receptor 4 (TLR4)) and nuclear factor kappaB (NF- κB)were determined compared among the groups.Results: At both 2 and 4 weeks, the expression of CIRP protein in the model group was significantly higher than that in the sham operation group (p < 0.05). At these two time-points, tumor formation and maximum diameter were higher in anti-CIRP and model control rats than in pseudo-operation rats. After 4 weeks of treatment, the protein expressions of TNF- α, MCP-1, TLR4 and NF-κB were higher in anti-CIRP and model control rats than in pseudo-operation rats, but were lower than model control values (p < 0.05).Conclusion: CIRP expression is significantly increased in abdominal aortic aneurysm tissue and serum, and is involved in the onset and progress of abdominal aortic aneurysm. Anti-CIRP antibody therapy effectively suppresses tumorigenesis, and inhibits tumor wall inflammatory reaction viaTLR4/NF-κB pathway. This finding provides a clue and new strategy for the clinical management of abdominal aortic aneurysm. Keywords: CIRP, Abdominal aortic tumor wall, Inflammatory reaction, Protein expression, Tumor body

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