scholarly journals Homocysteine-Enhanced Proteolytic and Fibrinolytic Processes in Thin Intraluminal Thrombus and Adjacent Wall of Abdominal Aortic Aneurysm: Study In Vitro

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Aldona Siennicka ◽  
Marta Zuchowski ◽  
Kornel Chełstowski ◽  
Miłosław Cnotliwy ◽  
Jeremy Simon Clark ◽  
...  
Keyword(s):  
Aortic Aneurysms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Sections ◽  
Control Tissue ◽  
Abdominal Aortic ◽  
Series Of Experiments ◽  
Positive Correlations ◽  
Adjacent Wall ◽  
Increased Activity

Homocysteine (Hcy) may affect the pathogenesis of abdominal aortic aneurysms (AAAs) through enhancement of proteolysis and an impaired coagulation/fibrinolysis system. Intensified haemostatic capacity may promote local proteolytic degradation of the aortic wall. This study aimed to examine the effects of Hcy on haemostatic and proteolytic processes in samples of thick and thin fragments of the ILT and underlying walls.Subjects and Methods. Thirty-six patients who underwent AAA surgery were enrolled. Aneurysm tissue sections were incubated with DL-Hcy (100 and 500μmol/L) in a series of experiments and analyzed for concentration/activity of proteolytic and haemostatic markers by enzyme-linked immunosorbent assay.Results. Incubation of wall underlying thin ILT segments (B) with DL-Hcy resulted in an increase of active MMP-2 levels compared to control tissue (9.54 ± 5.88 versus 7.44 ± 4.48, p=0.011). DL-Hcy also induced t-PA and plasminogen concentration increases in thin thrombus sections (B1) compared to control tissue (respectively: 1.39 ± 1.65 versus 0.84 ± 0.74, p=0.024; 11.64 ± 5.05 versus 10.34 ± 5.52, p=0.018). In contrast, wall adjacent to thick thrombus segments (A) showed decreases in MMP-2 and TF activities compared to control (respectively, 5.89 ± 3.39 versus 7.26 ± 5.49, p=0.046; 67.13 ± 72.59 versus 114.46 ± 106.29, p=0.007). In thick ILT sections (A1), DL-Hcy decreased MMP-2 activity and t-PA and plasminogen concentrations compared to control tissue (respectively, 2.53 ± 2.02 versus 3.28 ± 2.65, p=0.006; 0.67 ± 0.57 versus 0.96 ± 0.91, p=0.021; 9.25 ± 4.59 versus 12.63 ± 9.56, p=0.017). In addition, analysis revealed positive correlations at all sites between activities/concentrations of MMP-2, TF, and PAI-1 measured in control tissues and after incubation with DL-Hcy.Conclusions. These data indicate the potential for excess Hcy to enhance damage of arterial wall in thinner AAA segments as a result of the increased activity of MMP-2 and fibrinolytic factors.

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.

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

Neuronal NOS contributes to biphasic autoregulatory response during enhanced TGF activity

1999 ◽  
Vol 277 (1) ◽  
pp. F113-F120 ◽  
Author(s):  
Atsuhiro Ichihara ◽  
L. Gabriel Navar
Keyword(s):  
Initial Response ◽  
Renal Perfusion ◽  
Tubuloglomerular Feedback ◽  
Afferent Arterioles ◽  
Series Of Experiments ◽  
Oxide Synthase ◽  
Increased Activity ◽  
Arteriolar Diameter ◽  
Distal Delivery

To assess the afferent arteriolar autoregulatory response during increased activity of the tubuloglomerular feedback (TGF) mechanism and to delineate the contribution of neuronal nitric oxide synthase (nNOS) to this response, afferent arteriolar diameter responses to changes in renal perfusion pressure (RPP) were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. At RPP of 100 mmHg, basal afferent arteriolar diameter averaged 21.1 ± 1.4 μm ( n = 9). The initial and sustained constrictor responses of afferent arterioles to a 60-mmHg increase in RPP averaged 14.8 ± 1.4% and 13.3 ± 1.3%, respectively. Acetazolamide treatment, which enhances TGF responsiveness by increasing distal nephron volume delivery, significantly decreased basal afferent arteriolar diameter by 8.2 ± 0.5% and enhanced the initial response (25.5 ± 2.3%) to a 60-mmHg increase in RPP but did not alter the sustained response (14.3 ± 1.5%). In another series of experiments, nNOS inhibition with 10 μM S-methyl-l-thiocitrulline (l-SMTC) significantly decreased afferent arteriolar diameter from 20.3 ± 1.3 to 18.3 ± 1.1 μm ( n = 7) and enhanced both the initial (34.4 ± 3.5%) and sustained constrictor responses (27.6 ± 2.9%) to a 60-mmHg increase in RPP. Treatment with acetazolamide further enhanced both initial (56.4 ± 3.0%) and sustained responses (54.6 ± 2.7%). Interruption of distal delivery by transection of the loops of Henle prevented the enhanced responses to increases in RPP elicited with either acetazolamide orl-SMTC. These results indicate that nNOS contributes to the counteracting resetting process of biphasic afferent arteriolar constrictor responses to increases in RPP through a TGF-dependent mechanism.

The Development of Physiological Compliant Abdominal Aortic Aneurysm Models for In Vitro Flow Studies

2009 ◽  
Author(s):  
Timothy J. Corbett ◽  
Barry J. Doyle ◽  
Anthony Callanan ◽  
Tim M. McGloughlin
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Material Properties ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Flow Loop ◽  
The Past ◽  
Abdominal Aortic

A vast amount of experimental research has been undertaken in the past decade to investigate different aspects of preoperative and postoperative abdominal aortic aneurysms (AAAs). Much of this research has been based on the use of mock arteries in an in vitro flow loop to mimic the behaviour of the abdominal aorta in vivo [1]. These models should be reproducible, have consistent material properties, consistent thickness and be physiological in behaviour.

Real-Time Measurement of Multi-Component Velocity Vectors Within Abdominal Aortic Aneurysms Using Echo PIV: Comparison of In Vitro and Computational Results

2007 ◽  
Author(s):  
Lingli Liu ◽  
Fuxing Zhang ◽  
Rui Wang ◽  
Robin Shandas
Keyword(s):  
Disease Process ◽  
Abdominal Aortic Aneurysms ◽  
The United States ◽  
Aneurysm Rupture ◽  
Aortic Aneurysms ◽  
Non Invasive ◽  
Abdominal Aortic ◽  
Component Velocity ◽  
Aneurysm Growth

Abdominal aortic aneurysms (AAAs) are localized balloon-shaped expansions commonly found in the infrarenal segment of the abdominal aorta, between the renal arteries and the iliac bifurcation. Abdominal aortic aneurysm rupture has been estimated to occur in as much as 3%–9% of the population, and represents the 13th leading cause of death in the United States, producing more than 10,000 deaths annually [1]. Thus, determining the significant factors for aneurysm growth and rupture has become an important clinical goal. From a biomechanical standpoint, AAA rupture risk is related to certain mechanical and hemodynamic factors such as localized flow fields and velocity patterns, and flow-induced stresses within the fluid and in the aneurysm structure [2]. Disturbed flow patterns at different levels have also been found to trigger responses within medial and adventitial layers by altering intercellular communication mechanisms. Thus, localized hemodynamics proximal, within and distal to AAA formations play an important role in modulating the disease process, and non-invasive and easy-to-implement methods to characterize and quantify these complex hemodynamics would be tremendously useful.

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.

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.

Plasma Matrix Metalloproteinase Levels Do Not Predict Tissue Levels in Abdominal Aortic Aneurysms Suitable for Elective Repair

Vascular ◽  
2008 ◽  
Vol 16 (5) ◽  
pp. 248-252 ◽  
Author(s):  
W. Richard W. Wilson ◽  
Edward C. Choke ◽  
Joseph Dawson ◽  
Ian M. Loftus ◽  
Matthew M. Thompson
Keyword(s):  
Matrix Metalloproteinase ◽  
Aortic Aneurysms ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Levels ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Elective Repair ◽  
Circulating Levels ◽  
Aneurysm Diameter

The role of matrix metalloproteinases (MMPs) in abdominal aortic aneurysm (AAA) pathogenesis is well described. However, a clear role for the MMPs in disease prediction has not been established. The aim of this study was to determine if circulating levels of MMPs correlated with AAA diameter and with MMP concentrations within the aneurysm wall. Preoperative plasma samples and intraoperative infrarenal AAA sac biopsies were taken in a standard fashion from 31 patients undergoing elective repair. The concentrations of MMP-1, MMP-2, MMP-3, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2 were quantified in plasma and aneurysm wall homogenates using enzyme-linked immunosorbent assay. Comparison used the Spearman correlation. There were no correlations between the paired plasma and aneurysm wall concentrations for any MMP or TIMP. Correlation between MMP-9 levels in the aneurysm wall and aneurysm diameter was negative ( r = −.42, p = .019). Other correlations between plasma and tissue levels with aneurysm diameter were nonsignificant.

scholarly journals Cyclic nucleotide phosphodiesterase 1C contributes to abdominal aortic aneurysm

2021 ◽  
Vol 118 (31) ◽  
pp. e2107898118
Author(s):  
Chongyang Zhang ◽  
Hongmei Zhao ◽  
Yujun Cai ◽  
Jian Xiong ◽  
Amy Mohan ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cyclic Nucleotide ◽  
Aortic Aneurysms ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Causative Role ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is characterized by aorta dilation due to wall degeneration, which mostly occurs in elderly males. Vascular aging is implicated in degenerative vascular pathologies, including AAA. Cyclic nucleotide phosphodiesterases, by hydrolyzing cyclic nucleotides, play critical roles in regulating vascular structure remodeling and function. Cyclic nucleotide phosphodiesterase 1C (PDE1C) expression is induced in dedifferentiated and aging vascular smooth muscle cells (SMCs), while little is known about the role of PDE1C in aneurysm. We observed that PDE1C was not expressed in normal aorta but highly induced in SMC-like cells in human and murine AAA. In mouse AAA models induced by Angiotensin II or periaortic elastase, PDE1C deficiency significantly decreased AAA incidence, aortic dilation, and elastin degradation, which supported a causative role of PDE1C in AAA development in vivo. Pharmacological inhibition of PDE1C also significantly suppressed preestablished AAA. We showed that PDE1C depletion antagonized SMC senescence in vitro and/or in vivo, as assessed by multiple senescence biomarkers, including senescence-associated β-galactosidase activity, γ-H2AX foci number, and p21 protein level. Interestingly, the role of PDE1C in SMC senescence in vitro and in vivo was dependent on Sirtuin 1 (SIRT1). Mechanistic studies further showed that cAMP derived from PDE1C inhibition stimulated SIRT1 activation, likely through a direct interaction between cAMP and SIRT1, which leads to subsequent up-regulation of SIRT1 expression. Our findings provide evidence that PDE1C elevation links SMC senescence to AAA development in both experimental animal models and human AAA, suggesting therapeutical significance of PDE1C as a potential target against aortic aneurysms.

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