In vivo transfer of cholesterol from plasma into human aortic tissue

1987 ◽  
Vol 47 ◽  
pp. 21-29 ◽  
Author(s):  
Steen Stender ◽  
Erik Hjelms
Keyword(s):  
Aortic Tissue

The effect of angiotensin II on in vivo albumin transport in normal rabbit aortic tissue

1982 ◽  
Vol 44 (3) ◽  
pp. 307-318 ◽  
Author(s):  
Larry A. Feig ◽  
Nikolaos A. Peppas ◽  
Clark K. Colton ◽  
Kenneth A. Smith ◽  
Robert S. Lees
Keyword(s):  
Angiotensin Ii ◽  
Aortic Tissue

scholarly journals Engineering Silicone Rubbers for In Vitro Studies: Creating AAA Models and ILT Analogues With Physiological Properties

2009 ◽  
Vol 132 (1) ◽  
Author(s):  
T. J. Corbett ◽  
B. J. Doyle ◽  
A. Callanan ◽  
M. T. Walsh ◽  
T. M. McGloughlin
Keyword(s):  
In Vitro Studies ◽  
In Vivo Studies ◽  
Aortic Tissue ◽  
Element Analysis ◽  
Future Design ◽  
Change Behavior ◽  
Physiological Properties ◽  
Diameter Change

In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogs are used to mimic the in vivo AAA. While the models used may be physiological, their properties are frequently either not reported or investigated. This study is concerned with the testing and characterization of previously used vessel analog materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection molding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance), the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared with published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure-diameter change behavior of the models could be predicted numerically. ILT analogs were also manufactured and characterized. Ideal models were manufactured with ILT analog internal to the aneurysm region, and the effect of the ILT analog on the model compliance and stiffness was investigated. The wall materials had similar properties (Einit 2.22 MPa and 1.57 MPa) to aortic tissue at physiological pressures (1.8 MPa (from literature)). ILT analogs had a similar Young’s modulus (0.24 MPa and 0.33 MPa) to the medial layer of ILT (0.28 MPa (from literature)). All models had aneurysm sac compliance (2.62–8.01×10−4/mm Hg) in the physiological range (1.8–9.4×10−4/mm Hg (from literature)). The necks of the AAA models had similar stiffness (20.44–29.83) to healthy aortas (17.5±5.5 (from literature)). Good agreement was seen between the diameter changes due to pressurization in the experimental and FEA wall models with a maximum difference of 7.3% at 120 mm Hg. It was also determined that the inclusion of ILT analog in the sac of the models could have an effect on the compliance of the model neck. Ideal AAA models with physiological properties were manufactured. The behavior of these models due to pressurization was predicted using finite element analysis, validating this technique for the future design of realistic physiological AAA models. Addition of ILT analogs in the aneurysm sac was shown to affect neck behavior. This could have implications for endovascular AAA repair due to the importance of the neck for stent-graft fixation.

scholarly journals Pioglitazone Attenuates Injury-Induced Neointima Formation in Mouse Femoral Artery Partially through the Activation of AMP-Activated Protein Kinase

Pharmacology ◽  
2017 ◽  
Vol 100 (1-2) ◽  
pp. 64-73 ◽  
Author(s):  
Islam Osman ◽  
Arwa Fairaq ◽  
Lakshman Segar
Keyword(s):  
Protein Kinase ◽  
Femoral Artery ◽  
Immunoblot Analysis ◽  
Inhibitory Effect ◽  
Aortic Tissue ◽  
Neointima Formation ◽  
Vsmc Proliferation ◽  
Compound C ◽  
Amp Activated Protein Kinase

Background/Aims: Pioglitazone (PIO), an antidiabetic drug, has been shown to attenuate vascular smooth muscle cell (VSMC) proliferation, which is a major event in atherosclerosis and restenosis after angioplasty. Till date, the likely contributory role of AMP-activated protein kinase (AMPK) toward PIO inhibition of VSMC proliferation has not been examined in vivo. This study is aimed at determining whether pharmacological inhibition of AMPK would prevent the inhibitory effect of PIO on neointima formation in a mouse model of arterial injury. Methods: Male CJ57BL/6J mice were subjected to femoral artery injury using guidewire. PIO (20 mg/kg/day) was administered orally 1 day before surgery and for 3 weeks until sacrifice in the absence or presence of compound C (an AMPK inhibitor). Injured femoral arteries were used for morphometric analysis of neointima formation. Aortic tissue lysates were used for immunoblot analysis of phosphorylated AMPK. Results: PIO treatment resulted in a significant decrease in intima-to-media ratio by ∼50.3% (p < 0.05, compared with vehicle control; n = 6), which was accompanied by enhanced phosphorylation of AMPK by ∼85% in the vessel wall. Compound C treatment led to a marked reduction in PIO-mediated inhibition of neointima formation. Conclusion: PIO attenuates injury-induced neointima formation, in part, through the activation of AMPK.

Measurement of the absolute synthesis of soluble and insoluble elastin by chick aortic tissue

1983 ◽  
Vol 61 (10) ◽  
pp. 1079-1084 ◽  
Author(s):  
Fred W. Keeley ◽  
Dorothy J. Johnson
Keyword(s):  
Significant Proportion ◽  
State Level ◽  
Aortic Tissue ◽  
In Vitro Synthesis ◽  
Stage Of Development ◽  
Absolute Synthesis ◽  
Rate Of Accumulation ◽  
In Vivo Synthesis

The rate of in vitro synthesis of soluble and insoluble elastin by thoracic aorta of 2-day-old chicks has been measured in absolute terms. In the absence of β-aminopropionitrile (βAPN), the steady state level of soluble elastin was 120 pmol/100 mg of aortic tissue or 3.7 μg/whole aorta segment. The rate of synthesis of elastin in vitro was approximately 130 μg/day per whole aorta segment. This is three- to four-fold lower than the estimated rate of in vivo synthesis for a comparable segment of aortic tissue at the same stage of development. Pulse-chase experiments suggested that this difference was not due to in vitro proteolysis of a significant proportion of the newly synthesized soluble elastin, but rather that the conversion of soluble to insoluble elastin was both rapid and efficient. These experiments also indicated the presence in aortic tissue of a substantial pool of elastin of intermediate solubility. Although inclusion of βAPN in the incubation medium resulted in an increase in the amount of soluble elastin in aortic tissue, the rate of accumulation of newly synthesized soluble elastin in the presence of this inhibitor of cross-linking was not linear, but decreased with incubation time. Furthermore, although βAPN effectively suppressed the appearance of insoluble elastin for at least 2 h, some escape from the effect of this inhibitor was seen with further incubation. In general, βAPN significantly depressed elastin synthesis.

scholarly journals Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Beenish Majeed ◽  
Supannikar Tawinwung ◽  
Lance S. Eberson ◽  
Timothy W. Secomb ◽  
Nicolas Larmonier ◽  
...  
Keyword(s):  
T Cells ◽  
Angiotensin Ii ◽  
Regulatory T Cells ◽  
Immune Complex ◽  
T Lymphocyte ◽  
Interleukin 2 ◽  
Vascular Stiffness ◽  
Aortic Tissue ◽  
Lymphocyte Function

Adaptive immune function is implicated in the pathogenesis of vascular disease. Inhibition of T-lymphocyte function has been shown to reduce hypertension, target-organ damage, and vascular stiffness. To study the role of immune inhibitory cells, CD4+CD25+Foxp3+regulatory T cells (Tregs), on vascular stiffness, we stimulated the proliferation of Treg lymphocytesin vivousing a novel cytokine immune complex of Interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody clone JES6-1 (mAbCD25). Three-month-old male C57BL/6J mice were treated with IL-2/mAbCD25concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val5]angiotensin II. Our results indicate that the IL-2/mAbCD25complex effectively induced Treg phenotype expansion by 5-fold in the spleens with minimal effects on total CD4+and CD8+T-lymphocyte numbers. The IL-2/mAbCD25complex inhibited angiotensin II-mediated aortic collagen remodeling and the resulting stiffening, analyzed within vivopulse wave velocity and effective Young’s modulus. Furthermore, the IL-2/mAbCD25complex suppressed angiotensin II-mediated Th17 responses in the lymphoid organs and reduced gene expression of IL-17 as well as T cell and macrophage infiltrates in the aortic tissue. This study provides data that support the protective roles of Tregs in vascular stiffening and highlights the use of the IL-2/mAbCD25complex as a new potential therapy in angiotensin II-related vascular diseases.

scholarly journals Amyloid-Targeting PET Tracer [18F]Flutemetamol Accumulates in Atherosclerotic Plaques

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1072 ◽  
Author(s):  
Sanna Hellberg ◽  
Johanna Silvola ◽  
Heidi Liljenbäck ◽  
Max Kiugel ◽  
Olli Eskola ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Mouse Strains ◽  
Aortic Tissue ◽  
Atherosclerotic Plaques ◽  
Carotid Artery Plaque ◽  
Pet Tracer ◽  
Pet Ct ◽  
Human Carotid

Atherosclerosis is characterized by the accumulation of oxidized lipids in the artery wall, which triggers an inflammatory response. Oxidized low-density lipoprotein (ox-LDL) presents amyloid-like structural properties, and different amyloid species have recently been recognized in atherosclerotic plaques. Therefore, we studied the uptake of the amyloid imaging agent [18F]Flutemetamol in atherosclerotic plaques. The binding of [18F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II/LDLR−/−ApoB100/100 mice and C57BL/6N controls. Tracer biodistribution was studied in vivo with PET/CT, and ex vivo by gamma counter and digital ex vivo autoradiography. The presence of amyloid, ox-LDL, and macrophages in the plaques was examined by immunohistochemistry. [18F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II/LDLR−/−ApoB100/100 mice showed large thioflavin-S-positive atherosclerotic plaques containing ox-LDL and macrophages. Autoradiography revealed 1.7-fold higher uptake in the plaques than in a lesion-free vessel wall, but no difference in aortic tissue uptake between mouse strains were observed in the in vivo PET/CT. In conclusion, [18F]Flutemetamol binds to amyloid-positive areas in human atherosclerotic plaques. Further studies are warranted to clarify the uptake mechanisms, and the potential of the tracer for in vivo imaging of atherosclerosis in patients.

scholarly journals Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

2020 ◽  
Vol 61 (12) ◽  
pp. 1764-1775
Author(s):  
Jiayan Guo ◽  
Hanbing Mei ◽  
Zhen Sheng ◽  
Qingyuan Meng ◽  
Murielle M. Véniant ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cell Model ◽  
Pathogenic Mutation ◽  
Mapk Signaling ◽  
Aortic Tissue ◽  
Aortic Endothelial Cells ◽  
Apoptotic Pathways ◽  
Tissue Specimens

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-κB and p38/MAPK signaling pathways.

Abstract 474: Early Events in Dissecting Aneurysms Induced by Angiotensin-II Infusion: The Geometry-Driven Aspect of a Multifaceted Problem

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Lydia Aslanidou ◽  
Bram Trachet ◽  
Mauro Ferraro ◽  
Alessandra Piersigilli ◽  
Rodrigo Fraga-Silva ◽  
...  
Keyword(s):  
Finite Element ◽  
Angiotensin Ii ◽  
Ex Vivo ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Aortic Tissue ◽  
Isotropic Resolution ◽  
Circumferential Distribution ◽  
Dissecting Aneurysms

While research on dissecting aneurysms in Angiotensin-II infused mice spans more than a decade, the temporal sequence of initial events still remains unclear. Recent findings in our group suggested that focal medial tears at the vicinity of suprarenal side branches are the primary event in disease formation. In this study we used a combined experimental-computational approach to investigate the hypothesis that initial events of dissecting AAAs originate at branching sites along the aorta. Male apolipoprotein-deficient mice were infused with Angiotensin-II (n=11) and saline 0.9% (n=6) for 3 days and scanned with contrast-enhanced microCT prior to sacrifice. One animal presented an in-vivo rupture during the microCT scan, and was rescanned after 2.5 hours to observe real-time morphological changes. In all other animals, the excised aortic tissue was imaged with Phase Contrast X-Ray Tomographic Microscopy (PCXTM) at 6.5um isotropic resolution. An automatic morphing code was developed to map the ex-vivo geometry onto the in vivo geometry, and a finite element simulation yielded a stress distribution that represents an estimation of the wall tension, not only due to the pressurization, but also due to the local stretch field. We found that the nanoparticulate microCT contrast agent had infiltrated the aortic wall in 11/11 Ang-II infused animals, while no infiltration was observed in 6/6 control mice. The infiltration affected at least one pair of intercostal arteries in 11/11 mice, and in 9/11 mice the coeliac region was also affected. Image-guided histology allowed us to determine the circumferential distribution of microlesions at branching sites, including disruption of elastin fibers, apoptotic cell appearance, subintimal leukocyte infiltration and intramural hematomas. In the animal whose aorta had ruptured during the in vivo scan, the initial hematoma had originated around 3 pairs of intercostal arteries and quickly propagated afterwards. Mouse-specific finite element simulations revealed a co-location of computed peak stresses at the vessel wall and histologically identified vascular damage. We conclude that the aortic geometry, and side branches in particular, play a pivotal role in the onset of dissecting AAA.

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