The von Willebrand Pig as a Model for Atherosclerosis Research

1978 ◽  
Vol 39 (02) ◽  
pp. 322-327 ◽  
Author(s):  
V Fuster ◽  
E J W Bowie
Keyword(s):  
Arterial Wall ◽  
Atherosclerotic Plaques ◽  
Intimal Thickening ◽  
Cholesterol Diet ◽  
Ideal Model ◽  
Wall Interaction ◽  
A Prospective Study ◽  
Von Willebrand ◽  
Atherosclerosis Research ◽  
Single Lesion

SummaryIn order to evaluate a possible role played by platelets in the development of atherosclerosis, the aortas of 11 control pigs and 11 homozygous von Willebrand (vWd) pigs were examined for spontaneous atherosclerosis. Of the 11 normal pigs, 6 showed multiple atherosclerotic plaques with an intimal thickening of 63 to 130 μm. In contrast, none of the von Willebrand pigs had multiple plaques and only one showed a single lesion of more than 2 mm in diameter.In a prospective study 5 control pigs and 5 vWd pigs were given a high (2%) cholesterol diet from the age of 3 to 9 months. All of the controls developed atherosclerotic plaques. In 4 of the pigs the plaques exceeded 13% of the aortic surface with an intimal thickening of 50 to 390 pm. In contrast, only one of the vWd pigs developed atherosclerotic plaques which only involved 7% of the aortic surface. Most of the vWd pigs, however, developed non-atherosclerotic flat fatty lesions. These findings may be related to the imp aired platelet arterial wall interaction in vWd. The vWd pigs seem to be an ideal model for atherosclerosis research.

scholarly journals The von Willebrand Pig as a Model for Atherosclerosis Research

1977 ◽  
Author(s):  
V. Fuster ◽  
E. J. W. Bowie ◽  
J. C. Lewis
Keyword(s):  
Arterial Wall ◽  
Fatty Infiltration ◽  
Endothelial Damage ◽  
Blue Dye ◽  
Ideal Model ◽  
Wall Interaction ◽  
Von Willebrand ◽  
Relationship Of ◽  
Atherosclerosis Research ◽  
Single Lesion

The aortas of 11 pigs with homozygous von Willebrand’s disease (vWd) were compared with those of 11 normal pigs, all aged 1 to 3 years. Six of the controls exhibited multiple arteriosclerotic plaques over 2 mm. in diameter with intimal thickenings of 63 to 130 microns. In contrast, none of the vWd pigs had multiple plaques; one had a single lesion over 2 mm. in diameter.Ten additional pigs, 5 controls and 5 with homozygous vWd, were placed on a 2% cholesterol diet for 6 months, beginning at the age of 3 months. Four of the controls developed aortic arteriosclerotic lesions exceeding 7.5% of the entire surface. Intimal thickness ranged up to 370 microns. In contrast, 4 of the vWd pigs developed lesions not exceeding 0.5% of the aortic surface; the fifth vWd pig had arteriosclerotic lesions involving 7.3% of the aortic surface.The aortas of the vWd pigs did stain with Evans blue dye injected antemortem, and they exhibited fatty infiltration in the intima. By electron microscopy, severe endothelial damage was apparent, but there was no intimal proliferation.The vWd pig seems to be an ideal model for arteriosclerosis research and the possible relationship of our findings may be related to impaired platelet-arterial wall interaction in vWd.

Atherosclerosis in Homozygous and Heterozygous von Willebrand Pigs

1979 ◽  
Author(s):  
V. Fuster ◽  
E.J.W. Bowie ◽  
D.N. Fass
Keyword(s):  
Factor Viii ◽  
Rank Test ◽  
High Cholesterol Diet ◽  
Atherosclerotic Plaques ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Moderate Reduction ◽  
Factor Viii Antigen ◽  
Von Willebrand

We have reported that pigs with severe homozygous von Willebrand’s (vW) disease are resistant to spontaneous and high cholesterol diet-induced atherosclerosis. In this study we report the incidence and quantitation of aortic fibrous atherosclerotic plaques in three groups of pigs fed with a high (2%) cholesterol diet from age 3 to 9 months. Normal pigs (normal factor VIII antigen - VIII R:AG and ristocetin co-factor - VIII:RWF). Of 11 pigs, 8 (73%) had significant plaques involving more than 3% (mean 7.6%) of the aortic surface. Homozygous vW pigs (undetected VIII R:AG and VIII:RWF). None of the 7 pigs had significant plaques involving more than 3% of the aortic surface (p<0.01, rank ≤ test). Heterozygous_vW pigs (approximately 40% VIII R:AG and VIII.RWF). Of the 5 pigs, 3 (60%) had significant plaques involving more than 3% (mean 7.7%) of the aortic surface, the results not being significantly different from those obtained in the normal pig.This study suggests that resistance to atherosclerosis is not found in animals with moderate reduction of VIII R:AG and VIII:RWF. This might have implications in man since in human vW disease both factors are almost always present to some degree.

Interventional Thermal Injury of the Arterial Wall: Unfolding of von Willebrand Factor and Its Increased Binding to Collagen after 55° C Heating

1996 ◽  
Vol 75 (03) ◽  
pp. 515-519 ◽  
Author(s):  
Mark J Post ◽  
Anke N de Graaf-Bos ◽  
George Posthuma ◽  
Philip G de Groot ◽  
Jan J Sixma ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Conformational Changes ◽  
Arterial Wall ◽  
Platelet Adhesion ◽  
Type I ◽  
Temperature Dependent ◽  
Collagen Types ◽  
Electron Microscopic ◽  
Von Willebrand ◽  
Willebrand Factor

Summary Purpose. Thermal angioplasty alters the thrombogenicity of the arterial wall. In previous studies, platelet adhesion was found to increase after heating human subendothelium to 55° C and decrease after heating to 90° C. In the present electron microscopic study, the mechanism of this temperature-dependent platelet adhesion to the heated arterial wall is elucidated by investigating temperature-dependent conformational changes of von Willebrand factor (vWF) and collagen types I and III and the binding of vWF to heated collagen. Methods. Purified vWF and/or collagen was applied to electron microscopic grids and heated by floating on a salt-solution of 37° C, 55° C or 90° C for 15 s. After incubation with a polyclonal antibody against vWF and incubation with protein A/gold, the grids were examined by electron microscopy. Results. At 37° C, vWF was coiled. At 55° C, vWF unfolded, whereas heating at 90° C caused a reduction in antigenicity. Collagen fibers heated to 37° C were 60.3 ± 3.1 nm wide. Heating to 55° C resulted in the unwinding of the fibers, increasing the width to 87.5 ± 8.2 nm (p < 0.01). Heating to 90° C resulted in denatured fibers with an enlarged width of 85.1 ± 6.1 nm (p < 0.05). Heating of collagen to 55° C resulted in an increased vWF binding as compared to collagen heated to 37° C or to 90° C. Incubation of collagen with vWF, prior to heating, resulted in a vWF binding after heating to 55° C that was similar to the 37° C binding and a decreased binding after 90° C. Conclusions. After 55° C heating, the von Willebrand factor molecule unfolds and collagen types I and III exhibit an increased adhesiveness for von Willebrand factor. Heating to 90° C denatures von Willebrand factor and collagen. The conformation changes of von Willebrand factor and its altered binding to collagen type I and III may explain the increased and decreased platelet adhesion to subendothelium after 55° C and 90° C heating, respectively.

scholarly journals Prophylaxis escalation in severe von Willebrand disease: a prospective study from the von Willebrand Disease Prophylaxis Network

2015 ◽  
Vol 13 (9) ◽  
pp. 1585-1589 ◽  
Author(s):  
T. Abshire ◽  
J. Cox‐Gill ◽  
C. L. Kempton ◽  
F. W. G. Leebeek ◽  
M. Carcao ◽  
...  
Keyword(s):  
Prospective Study ◽  
Von Willebrand Disease ◽  
A Prospective Study ◽  
Von Willebrand

Simvastatin Reduces Expression and Activity of Lipoprotein-Associated Phospholipase A2 in the Aorta of Hypercholesterolaemic Atherosclerotic Rabbits

2009 ◽  
Vol 37 (4) ◽  
pp. 1029-1037 ◽  
Author(s):  
Z Qiao ◽  
J Ren ◽  
H Chen
Keyword(s):  
Atherosclerotic Lesion ◽  
Statin Treatment ◽  
Control Group ◽  
High Cholesterol Diet ◽  
Atherosclerotic Plaques ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Local Inflammatory Response ◽  
Plaque Instability ◽  
Significant Difference

Lipoprotein-associated phospholipase A2 (Lp-PLA2) contributes to atherosclerotic plaque instability and subsequent sudden coronary death. Statins are associated with decreased stroke risk and may improve stability of atherosclerotic plaques. The present study investigated the effect of simvastatin on expression of Lp-PLA2 levels in atherosclerotic plaques and on Lp-PLA2 activity in atherosclerotic aortas. Rabbits were a fed chow (control group) or a high-cholesterol diet (atherosclerosis group) for 12 weeks. An additional group on the high-cholesterol diet received simvastatin (5 mg/kg per day) for the last 4 weeks (simvastatin group). Lp-PLA2 activity in plasma and atherosclerotic aortas was significantly higher in the atherosclerosis group than in the control group and, consistent with this, abundant Lp-PLA2 protein was detected in plaques in the atherosclerosis group. Simvastatin significantly reduced Lp-PLA2 activity in plasma and aorta tissue, and reduced Lp-PLA2 protein level in atherosclerotic plaques. Whereas there was no significant difference in total atherosclerotic lesion area between simvastatin and atherosclerosis groups, simvastatin significantly reduced macrophage content, lipid retention and the intima/media ratio but increased the content of smooth muscle cells in atherosclerotic lesions. Thus, statin treatment markedly reduced Lp-PLA2 in both plasma and atherosclerotic plaques. This was associated with attenuation of the local inflammatory response and improved plaque stability.

Misinterpretation of the Functional Severity of Coronary Stenosis Due To Variability in Arterial Wall Compliance

2010 ◽  
Author(s):  
Bhaskar Chandra Konala ◽  
Ashish Das ◽  
Mohamed Effat ◽  
Arif Imran ◽  
Rupak K. Banerjee
Keyword(s):  
Arterial Wall ◽  
Coronary Intervention ◽  
Diagnostic Parameter ◽  
Carreau Model ◽  
Newtonian Viscosity ◽  
Coronary Stenoses ◽  
Wall Compliance ◽  
Wall Interaction ◽  
Stenotic Arteries ◽  
Parameter Values

Effect of arterial wall compliance on the invasive coronary diagnostic parameters for various severities of coronary stenoses was assessed. The Mooney-Rivlin model was used to define the non-linear properties of the arterial wall and the plaque regions. The non-Newtonian viscosity of blood was modeled using the Carreau model. A finite element method was employed to solve the pulsatile fluid (blood)-structure (arterial wall) interaction (FSI) equations. Variability in the diagnostic parameter values can occur near the cut-off value due to change in compliance of stenotic arteries between the range of 84% and 89% area stenosis. This may lead to misdiagnosis and might wrongly lead to postponement of coronary intervention.

A New 3D Reconstruction Method for Human Coronary Bifurcations for Shear Stress Computations

2012 ◽  
Author(s):  
Frank Gijsen ◽  
Hans Schuurbiers ◽  
Michiel Schaap ◽  
Anton van der Steen ◽  
Jolanda Wentzel
Keyword(s):  
Shear Stress ◽  
Coronary Arteries ◽  
Arterial Wall ◽  
Plaque Formation ◽  
Atherosclerotic Plaques ◽  
Reconstruction Method ◽  
Human Coronary Artery ◽  
Multislice Computer Tomography ◽  
Stress Influences ◽  
The Impact

Atherosclerosis is characterized by lipid accumulation in the arterial wall, followed by an inflammatory response. Plaque formation is generally observed near bifurcations in coronary arteries. The composition of atherosclerotic plaques depends on the location, and it was hypothesized that blood flow induced shear stress influences plaque composition2. To study the impact of shear stress on atherosclerotic disease in human coronary arteries, we developed a technique that enables us to generate 3D lumen reconstruction based on multislice computer tomography (MSCT) and intravascular ultrasound (IVUS).We describe two approaches to generate 3D reconstructions of human coronary artery bifurcations and apply them to coronary segments with bifurcations. We will evaluate the effect on shear stress distribution and its relationship to wall thickness.

Tumor Microvessel Density as a Predictor of Recurrence After Resection of Hepatocellular Carcinoma: A Prospective Study

2002 ◽  
Vol 20 (7) ◽  
pp. 1775-1785 ◽  
Author(s):  
Ronnie Tung-Ping Poon ◽  
Irene Oi-Lin Ng ◽  
Cecilia Lau ◽  
Wun-Ching Yu ◽  
Zhen-Fan Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Microvessel Density ◽  
Disease Free Survival ◽  
Postoperative Recurrence ◽  
Image Analyzer ◽  
Free Survival ◽  
A Prospective Study ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Disease Free

PURPOSE: This study prospectively evaluated the correlation of tumor microvessel density (MVD) with clinicopathologic features and postoperative recurrence in patients undergoing resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Tumor MVD was assessed in 100 patients with resection of HCC using a computer image analyzer after immunostaining for CD34 (MVD-CD34) and von Willebrand factor (MVD-vWF), respectively. Patients were prospectively followed for recurrence. RESULTS: Mean tumor MVD-CD34 (236/0.74 mm2) was higher than mean tumor MVD-vWF (87/0.74 mm2) (P < .001). By multiple regression analysis, tumor size was the only pathologic feature significantly related to tumor MVD-CD34. The median MVD-CD34 was 316/0.74 mm2 in HCCs ≤ 5 cm (n = 46) and 146/0.74 mm2 in HCCs more than 5 cm (n = 54) (P < .001). Among patients with HCCs ≤ 5 cm, those with higher than median MVD-CD34 had worse disease-free survival (at 3 years, 13%) than those with a lower MVD-CD34 (at 3 year, 74%) (P = .002). Multivariate analysis showed that tumor MVD-CD34 was the only significant factor predictive of disease-free survival in patients with HCC ≤ 5 cm. For HCCs more than 5 cm, MVD-CD34 did not have a significant prognostic influence. MVD-vWF did not have a significant prognostic influence on disease-free survival in either HCCs ≤ 5 cm or more than 5 cm. CONCLUSION: This study shows that a high MVD-CD34 was predictive of early postresection recurrence in patients with HCCs ≤ 5 cm and, therefore, may be a novel prognostic marker in this subset of patients.

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