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.

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.

Abstract 418: Microfibrillar-Associated Protein 4 Deficiency Reduces Size and Incidence Rate of Angiotensin II Induced Abdominal Aortic Aneurysms in Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Katrine L Kirketerp-Møller ◽  
Jane Stubbe ◽  
Anders Schlosser ◽  
Karin Kejling ◽  
Jesper B Møller ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Incidence Rate ◽  
Aortic Aneurysms ◽  
Aortic Tissue ◽  
Aortic Blood Flow ◽  
Infrarenal Aorta ◽  
Arterial Blood ◽  
Elastin Degradation ◽  
Abdominal Aortic

Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix (ECM) protein primarily located in elastic arteries. It can bind elastin and collagen, and furthermore activate vascular cells through cellular integrin binding and modulate matrix metalloprotinase (MMP) activity. We hypothesized that lack of MFAP4 would decrease vascular inflammation and abdominal aortic aneurysm (AAA) formation. AAA was induced in 9-11 week old mice using two experimental mouse models: 1) Male Mfap4 -/- /ApoE -/- double knock-out (dKO) and ApoE -/- littermate control mice were feed western diet and subjected to continuously angiotensin II (AngII, 1000 ng/kg/min) infusion for 9-28 days via subcutaneous osmotic mini-pumps. Arterial blood pressure was measured in the femoral artery. 2) 1.5 U/mL elastase was infused into the infrarenal aorta in Mfap4 -/- and littermate Mfap4 +/+ mice for 5 minutes. Aortic blood flow was restored and the mice recovered for 9-16 days. Aortic diameter was measured in mice subjected to AngII or elastase infusion at day 28 and 16 respectively. MMP activity was detected by zymography. No difference in AAA formation was observed between genotypes after elastase perfusion. In response to AngII infusion dKO mice showed a significantly decrease in AAA diameter and incidence rate compared to ApoE -/- mice. AngII-induced increase in blood pressure was not dependent of MFAP4. However, there was decreased aortic arch atherosclerotic plaque formation, MMP2 and MMP9 activity in aortic tissue from dKO mice compared to ApoE -/- mice. Furthermore there was a non-significant tendency of decreased elastin degradation score in the AngII infused dKO mice, however this was not observed in the elastase perfused mice. Activity of MMP12 and extent of infiltrating leukocytes in aneurysmal tissue from both models will be further investigated. In conclusion we observed a decreased AAA formation and MMP activity in Mfap4 -/- /ApoE -/- mice which was not explained by variation in blood pressure or altered elastin degradation. The data suggest that MFAP4 induces MMP2-activity and thus the propensity for AAA formation.

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.

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.

scholarly journals Ligation of the aorta for a mycotic abdominal aortic aneurysm in an infant

2018 ◽  
Vol 6 ◽  
pp. 2050313X1876130
Author(s):  
Zahira Zouizra ◽  
Soukaina Benbakh ◽  
Gaël Biaou ◽  
Drissi Boumzebra
Keyword(s):  
Mycotic Aneurysm ◽  
Aortic Aneurysms ◽  
Infrarenal Aorta ◽  
Limited Data ◽  
Short Term ◽  
Term Outcome ◽  
Short Term Outcome ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Mycotic aortic aneurysms are exceedingly uncommon in infants and they have a high risk of rupture. Their surgical management is extremely challenging. We report a case of a 22-month-old girl who presented with abdominal pain and fever revealing a ruptured mycotic aneurysm of the infrarenal aorta. The surgical treatment consisted of a ligature of the proximal and distal ends of the aneurysm. Postoperative course was significant for hypertension. A year and a half follow-up showed no other complications. Limited data are available concerning our chosen technique, but the reported cases showed a good short-term outcome.

A Review of the In Vivo and In Vitro Biomechanical Behavior and Performance of Postoperative Abdominal Aortic Aneurysms and Implanted Stent-Grafts

2008 ◽  
Vol 15 (4) ◽  
pp. 468-484 ◽  
Author(s):  
Timothy J. Corbett ◽  
Anthony Callanan ◽  
Liam G. Morris ◽  
Barry J. Doyle ◽  
Pierce A. Grace ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Stent Grafts ◽  
Biomechanical Behavior ◽  
Abdominal Aortic ◽  
And Performance

Towards the Prediction and Minimization of Device Failure for Endolvascular Grafts in Abdominal Aortic Aneurysms

2007 ◽  
Author(s):  
Ron Layman ◽  
Samy Missoum ◽  
Jonathan Vande Geest
Keyword(s):  
United States ◽  
Abdominal Aortic Aneurysm ◽  
Critical Diameter ◽  
Abdominal Aortic Aneurysms ◽  
The United States ◽  
Aortic Aneurysms ◽  
Infrarenal Aorta ◽  
Device Failure ◽  
Clinical Challenge ◽  
Abdominal Aortic

The local dilation of the infrarenal aorta, termed an abdominal aortic aneurysm (AAA), occurs over several years and may eventually lead to rupture, an event currently ranked the 15th leading cause of death in the United States [1, 2]. AAA can often remain quiescent and asymptomatic, making the diagnosis and treatment of AAA patients a clinical challenge. For patients whose AAAs dilate to a critical diameter there are two standard treatments: open surgical resection and endovascular repair (EVAR). EVAR involves inserting an endovascular graft into the aneurysm to prevent pressurization of the AAA cavity.

Mykotisches Aneurysma der infrarenalen Aorta

VASA ◽  
2003 ◽  
Vol 32 (4) ◽  
pp. 218-220 ◽  
Author(s):  
Papadimitriou ◽  
Tachtsi ◽  
Koutsias ◽  
Pitoulias ◽  
Mpompoti
Keyword(s):  
Relevant Literature ◽  
Aortic Aneurysms ◽  
Ex Situ ◽  
Infrarenal Aorta ◽  
Autologous Vein ◽  
Abdominal Aortic ◽  
Mycotic Aneurysms ◽  
Post Traumatic

The mycotic aneurysms of the infrarenal aorta (MAIA) are extremely rare and the associated morbidity and mortality is very high. The classification of infected aneurysms considers four types: a) true mycotic aneurysms, b) secondary mycotic aneurysms due to bacterial arteritis, c) infected preexisting abdominal aortic aneurysms and d) post-traumatic infected false aneurysms. The prognosis of true MAIA’s is better than the other forms of infected aneurysms. The standard treatment includes the resection of the aneurysm and infectious surrounding tissues and the restoration of the flow using ex situ (axillobifemoral) bypass or in situ replacement with autologous vein or a rifampicine-bonded graft. We present a case of mycotic aneurysm of the infrarenal aorta and a brief discussion of the alternative treatments from the relevant literature.

Morphometry and Classification in Abdominal Aortic Aneurysms: Patient Selection for Endovascular and Open Surgery

1997 ◽  
Vol 4 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Hardy Schumacher ◽  
Hans H. Eckstein ◽  
Friedrich Kallinowski ◽  
Jens Rainer Allenberg
Keyword(s):  
Patient Selection ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Type I ◽  
Infrarenal Aorta ◽  
Iliac Arteries ◽  
Proximal Neck ◽  
Aorta Aneurysm ◽  
Abdominal Aortic ◽  
Selection For

Purpose: To evaluate the anatomic morphology of abdominal aortic aneurysms (AAAs) and compose a classification system to facilitate patient selection for endovascular graft (EVG) repair. Methods: Data on 242 consecutive AAA patients evaluated on a nonemergent basis in a 3.5-year period to July 1996 were prospectively entered into a registry. Patients were examined using sequential intravenous spiral computed tomographic angiography and intraarterial digital subtraction angiography. The data collected and analyzed included: diameters of the supra- and infrarenal aorta, aneurysm, aortoiliac bifurcation, and iliac arteries; lengths of the proximal neck, distal cuff, and aneurysm; degrees of iliac artery tortuosity; and occlusion of the visceral, renal, or iliac arteries. Results: The 242 aneurysms could be easily grouped into three distinctive categories related to the extent of the aneurysmal disease. Type I AAAs (11.2%) had nondilated, thrombus-free infrarenal (15 mm) necks and distal (10 mm) cuffs appropriate for EVG anchoring. In type II and its subgroups (72.3%), a sufficient proximal neck was present, but the aneurysm extended into the iliac arteries; 56% of these were eligible for a bifurcated endograft. In type III (16.5%), a sufficient proximal neck was missing, independent of distal involvement. In all, 51.7% were good EVG candidates based on AAA morphology. Taking into consideration relevant concomitant vascular diseases, proximal iliac kinking, and iliac, renal, or visceral occlusive disease, only 30.2% of the population were potential candidates for an efficient and secure EVG repair using the devices currently available. Conclusions: In contrast to classical open repair, detailed preoperative measurements are recommended for EVG planning. The use of liberal EVG indications may lead to a higher incidence of complications, whereas restrictive morphology-based selection criteria may offer excellent results.

Elastin degradation in abdominal aortic aneurysms

1987 ◽  
Vol 65 (1-2) ◽  
pp. 13-21 ◽  
Author(s):  
J.S. Campa ◽  
R.M. Greenhalgh ◽  
Janet T. Powell
Keyword(s):  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Elastin Degradation ◽  
Abdominal Aortic
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