scholarly journals Recombinant Interleukin‐19 Suppresses the Formation and Progression of Experimental Abdominal Aortic Aneurysms

2021 ◽  
Author(s):  
Hiroki Tanaka ◽  
Baohui Xu ◽  
Haojun Xuan ◽  
Yingbin Ge ◽  
Yan Wang ◽  
...  
Keyword(s):  
Aortic Aneurysms ◽  
Matrix Metalloproteinase 2 ◽  
Cytotoxic T Cell ◽  
Alternatively Activated Macrophages ◽  
Elastin Degradation ◽  
Abdominal Aortic ◽  
Immunosuppressive Cytokine ◽  
Aneurysm Repair ◽  
Oxide Synthase

Background Interleukin‐19 is an immunosuppressive cytokine produced by immune and nonimmune cells, but its role in abdominal aortic aneurysm (AAA) pathogenesis is not known. This study aimed to investigate interleukin‐19 expression in, and influences on, the formation and progression of experimental AAAs. Methods and Results Human specimens were obtained at aneurysm repair surgery or from transplant donors. Experimental AAAs were created in 10‐ to 12‐week‐old male mice via intra‐aortic elastase infusion. Influence and potential mechanisms of interleukin‐19 treatment on AAAs were assessed via ultrasonography, histopathology, flow cytometry, and gene expression profiling. Immunohistochemistry revealed augmented interleukin‐19 expression in both human and experimental AAAs. In mice, interleukin‐19 treatment before AAA initiation via elastase infusion suppressed aneurysm formation and progression, with attenuation of medial elastin degradation, smooth‐muscle depletion, leukocyte infiltration, neoangiogenesis, and matrix metalloproteinase 2 and 9 expression. Initiation of interleukin‐19 treatment after AAA creation limited further aneurysmal degeneration. In additional experiments, interleukin‐19 treatment inhibited murine macrophage recruitment following intraperitoneal thioglycolate injection. In classically or alternatively activated macrophages in vitro, interleukin‐19 downregulated mRNA expression of inducible nitric oxide synthase, chemokine C‐C motif ligand 2, and metalloproteinases 2 and 9 without apparent effect on cytokine‐expressing helper or cytotoxic T‐cell differentiation, nor regulatory T cellularity, in the aneurysmal aorta or spleen of interleukin‐19–treated mice. Interleukin‐19 also suppressed AAAs created via angiotensin II infusion in hyperlipidemic mice. Conclusions Based on human evidence and experimental modeling observations, interleukin‐19 may influence the development and progression of AAAs.

The Potential of AFX Iliac Extension in Abdominal Aortic Aneurysms with High Iliac Tortuosity

2021 ◽  
Author(s):  
Yuta Kikuchi ◽  
Norifumi Ohtani ◽  
Hiroyuki Kamiya
Keyword(s):  
Aortic Aneurysm ◽  
Circulatory System ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Silicon Tube ◽  
Underwater Camera ◽  
Aneurysm Repair ◽  
Aortic Aneurysm Repair

Abstract Background Recently, endovascular aortic aneurysm repair (EVAR) is the most common surgery for abdominal aortic aneurysm (AAA). However, iliac limb complications of EVAR often cause problems in patients with high iliac tortuosity. There is no difference of rate of iliac limb complication among EVAR devices, such as Excluder, Endurant, and Zenith in high iliac tortuosity. But there has been not reported about AFX. Objectives We studied AFX iliac extension as it is the only stent graft with an endoskeletal framework. This study aimed to evaluate the AFX iliac extension patency in a case in vitro and to use it in seven cases of AAA with high iliac tortuosity. Methods The silicon tube inserted in the AFX iliac extension was flexed at 30, 60, 90, and 120 degrees, and the lumen of the iliac extension was monitored using an underwater camera in the circulatory system. During the experiment, the Iwaki Bellows Pump (IWAKI CO., LTD., Tokyo, Japan) produced a pulsating flow. We used this in seven patients with AAA high iliac tortuosity cases between November 2018 and May 2019. Results If the silicon tube inserted in the AFX iliac extension was flexed at 60 and 120 degrees, the stent protruded into the lumen. However, the graft was dilated at all degrees. All seven patients with AFX iliac extension had no complications and a patent iliac artery. Conclusion The AFX iliac extension can reduce iliac limb complications in cases of high iliac tortuosity.

Abstract 17136: MicroRNA-181b Inhibition Stabilises Abdominal Aortic Aneurysms by Promoting Collagen Accumulation and Elastin Deposition

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Karina Di Gregoli ◽  
Nur Najmi Mohamad Anuar ◽  
Sarah J George ◽  
Jason L Johnson
Keyword(s):  
Protein Expression ◽  
Collagen Fibre ◽  
Aortic Aneurysms ◽  
High Fat ◽  
Direct Role ◽  
Knockout Mouse Model ◽  
Elastin Degradation ◽  
Abdominal Aortic ◽  
Collagen Accumulation

Increased matrix metalloproteinase (MMP) activity, and related collagen and elastin degradation as a result of macrophage accumulation, are key characteristics of abdominal aortic aneurysm (AAA) progression and rupture. Accordingly targeting MMPs or promoting expression of the endogenous tissue inhibitor of metalloproteinases (TIMPs), may represent novel therapeutic strategies to prevent AAA progression and rupture. To closely mimic human AAA, we used an angiotensin II (AngII)-infused, high fat-fed apolipoprotein E knockout mouse model. Sudden death due to aortic dissection/rupture, was significantly increased (30%, p<0.001, n=20) in TIMP3 KO mice compared to wild-type controls, supporting a protective role for TIMP3 in AAA progression. Moreover Q-PCR revealed that microRNA (miR)-181b, a validated repressor of TIMP3 protein expression, was up-regulated 22-fold (n=6, p<0.001) in human AAA compared to non-aneurysmal sites. In vitro, miR181b inhibition increased macrophage TIMP3 protein expression 3-fold (n=4, p<0.05), highlighting miR181b inhibition as a potential approach to retard AAA progression. Indeed using a miR181b inhibitor, AAA development and inflammation was retarded in AngII-infused high fat-fed ApoE KO mice. This effect was characterised by a 56% reduction in macrophage content (n=5, p<0.05), augmented collagen content 1.9-fold (n=5, p<0.05) and collagen fibre thickness (+24%, p<0.05) in AAAs compared to scrambled-miR control animals. AAA elastin content was also increased (1.5-fold, n=5, p<0.05) in miR181b inhibitor treated mice versus controls. Collagen accumulation was TIMP-3 dependent as miR-181b inhibition did not affect collagen levels in TIMP-3 KO mice. However elastin content remained elevated in miR-181b inhibitor treated TIMP3 KO mice (2-fold, n=6, p=0.001), suggesting a TIMP-3 independent mechanism. In vitro miR181b inhibition in smooth muscle cells revealed a 2.5-fold increase in elastin production (n=3, p<0.05), supporting a direct role for miR-181b in elastin regulation. Collectively our data show that miR181b inhibition stabilises AAA through a dual beneficial effect, by promoting collagen preservation via TIMP3 modulation, and through directly increasing elastin production and deposition.

scholarly journals Vinpocetine protects against the development of experimental abdominal aortic aneurysms

2020 ◽  
Vol 134 (22) ◽  
pp. 2959-2976
Author(s):  
Chongyang Zhang ◽  
Chia George Hsu ◽  
Amy Mohan ◽  
Hangchuan Shi ◽  
Dongmei Li ◽  
...  
Keyword(s):  
Cerebrovascular Disorders ◽  
Degenerative Disease ◽  
Aortic Aneurysms ◽  
Infrarenal Aorta ◽  
Post Intervention ◽  
Aged Population ◽  
Elastin Degradation ◽  
Abdominal Aortic ◽  
Aneurysmal Dilation

Abstract Abdominal aortic aneurysm (AAA), commonly occurring in the aged population, is a degenerative disease that dilate and weaken infrarenal aorta due to progressive degeneration of aortic wall integrity. Vinpocetine, a derivative of alkaloid vincamine, has long been used for cerebrovascular disorders and cognitive impairment in the aged population. Recent studies have indicated that vinpocetine antagonizes occlusive vascular disorders such as intimal hyperplasia and atherosclerosis. However, its role in vascular degenerative disease AAA remains unexplored. Herein, we determined the effect of vinpocetine on the formation of AAA as well as the intervention of pre-existing moderate AAA. AAA was induced by periaortic elastase application in C57BL/6J mice. Systemic vinpocetine treatment was applied daily via intraperitoneal injection. We showed that vinpocetine pre-treatment remarkably attenuated aneurysmal dilation assessed by diameter and volume. More importantly, vinpocetine also significantly suppressed the progression of pre-existing moderate AAA in a post-intervention model. Vinpocetine improved multiple cellular and molecular changes associated with AAA, such as elastin degradation, media smooth muscle cell depletion, collagen fibers remodeling and macrophage infiltration in aneurysmal tissues. Vinpocetine potently suppressed tumor necrosis factor-α-induced nuclear factor kappa-light-chain-enhancer of activated B cells activation and proinflammatory mediator expression in primary cultured macrophages in vitro, as well as in the aorta wall in vivo, suggesting vinpocetine conferred anti-AAA effect at least partially via the inhibition of inflammation. Taken together, our findings reveal a novel role of vinpocetine in AAA formation, development and progression. Given the excellent safety profile of vinpocetine, the present study suggests vinpocetine may be a novel therapeutic agent for AAA prevention and treatment.

Efficacy and safety of doxycycline for the management of small abdominal aortic aneurysms- a meta analysis

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Abdul Razzack ◽  
D Rocha Castellanos ◽  
A Lopez Mendez ◽  
M Fernando Perez Paz ◽  
S Pothuru ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Abdominal Aortic Aneurysms ◽  
Abdominal Aortic Aneurysm Repair ◽  
Mean Difference ◽  
Aortic Aneurysms ◽  
Efficacy And Safety ◽  
Funding Sources ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Aneurysm Repair

Abstract Funding Acknowledgements Type of funding sources: None. Background- Patients with small Abdominal Aortic Aneurysms are managed with surveillance as there is currently insufficient evidence to recommend surgical aneurysm repair. Hence, there is a dire need and interest in pharmacotherapy like tetracycline antibiotics to reduce the need for aneurysm repair. Purpose- To determine the efficacy and safety of doxycycline in the management of small abdominal aortic aneurysms. Methods- Electronic databases (PubMed, Scopus, Embase, Cochrane) were searched until 25th November 2020.The primary outcomes were the mean difference (MD) in aneurysm diameter and the odds ratio (OR) calculated to compare the number of individuals referred to Abdominal aortic aneurysm repair in each group. Results- A total of three studies with 572 participants (Doxycycline = 290; Placebo = 282 ) were included in our analysis. Average follow up was a period of 18 months. For AAA expansion, the combined results demonstrated a statistically significant mean difference in expansion rates favoring the placebo groups over the intervention (WMD-0.75, 95%CI 0.12-1.38; p = 0.02;I2 = 0%) There was no statistically significant difference in the efficacy and safety of doxycycline as opposed to placebo groups for referral to AAA surgery (OR 1.01, 95%CI 0.61-1.69; p = 0.96, I2 = 0%) and all-cause mortality(OR 0.51; 95%CI 0.18-1.43; p = 0.20, I2 =0%) Conclusion- Amongst patients with small abdominal aortic aneurysms, doxycycline did not significantly reduce aneurysm growth. Abstract Figure. A) AAA expansion B)Surgery C)Mortality

scholarly journals The Impact of Endovascular Repair of Abdominal Aortic Aneurysms on Vascular Surgery Training in Open Aneurysm Repair

2021 ◽  
Vol 74 (3) ◽  
pp. e158-e159
Author(s):  
Nadin Elsayed ◽  
Maryam A. Khan ◽  
Isaac Naazie ◽  
Jaideep Das Gupta ◽  
Randall De Martino ◽  
...  
Keyword(s):  
Vascular Surgery ◽  
Endovascular Repair ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Surgery Training ◽  
Abdominal Aortic ◽  
Aneurysm Repair ◽  
The Impact

scholarly journals Unfavorable iliac artery anatomy causing access limitations during endovascular abdominal aortic aneurysm repair: application of the endoconduit technique

2014 ◽  
Vol 13 (4) ◽  
pp. 318-324
Author(s):  
Rodrigo Gibin Jaldin ◽  
Marcone Lima Sobreira ◽  
Regina Moura ◽  
Matheus Bertanha ◽  
Jamil Víctor de Oliveira Mariaúba ◽  
...  
Keyword(s):  
Iliac Artery ◽  
Endovascular Aneurysm Repair ◽  
Abdominal Aortic Aneurysms ◽  
Abdominal Aortic Aneurysm Repair ◽  
Aortic Aneurysms ◽  
Arterial Access ◽  
Abdominal Aortic ◽  
First Choice ◽  
Aneurysm Repair ◽  
Aortic Aneurysm Repair

Endovascular aneurysm repair (EVAR) is already considered the first choice treatment for abdominal aortic aneurysms (AAA). Several different strategies have been used to address limitations to arterial access caused by unfavorable iliac artery anatomy. The aim of this report is to illustrate the advantages and limitations of each option and present the results of using the internal endoconduit technique and the difficulties involved.

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.

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