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.

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 Endothelial Dysfunction Is Associated with Mortality and Severity of Coagulopathy in Patients with Sepsis and Disseminated Intravascular Coagulation

2019 ◽  
Vol 25 ◽  
pp. 107602961985216 ◽  
Author(s):  
Amanda Walborn ◽  
Matthew Rondina ◽  
Michael Mosier ◽  
Jawed Fareed ◽  
Debra Hoppensteadt
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Protein C ◽  
High Mobility ◽  
Severity Of Illness ◽  
Endothelial Activation ◽  
Endothelial Damage ◽  
Intravascular Coagulation ◽  
Angiopoietin 2 ◽  
Von Willebrand ◽  
Relationship Of

The role of the endothelium in sepsis-associated disseminated intravascular coagulation (DIC) is multifaceted and may contribute substantially to disease severity and outcome. The purpose of this study was to quantify measures of endothelial function, including markers of activation (endocan, Angiopoietin-2 [Ang-2], and von Willebrand Factor), endogenous anticoagulants (tissue factor pathway inhibitor and protein C), and damage-associated factors (High Mobility Group Box 1 [HMGB-1]) in the plasma of patients with sepsis and DIC, and to determine the relationship of these factors with severity of illness and outcome. Plasma samples were collected from 103 adult patients with sepsis within 48 hours of intensive care unit admission. Biomarker levels were measured using commercially available, standardized methods. Disseminated intravascular coagulation was diagnosed according to the International Society of Thrombosis and Hemostasis scoring algorithm. Twenty-eight-day mortality was used as the primary end point. In this study, endothelial damage and dysfunction were associated with the severity of coagulopathy and mortality in DIC patients. Loss of the endogenous anticoagulant protein C and elevation in the vascular regulator Ang-2 were associated with the development of overt DIC. In addition to Ang-2 and protein C, endocan, a biomarker of endothelial activation, and HMGB-1, a mediator of endothelial damage and activation, were significantly associated with mortality. This underscores the contribution of the endothelium to the pathogenesis of sepsis-associated DIC.

Following Mild Carotid Endothelial Injury, Platelet-Arterial Wall Interaction Is Impaired In Pigs With Von Willebrand'S Disease

1981 ◽  
Author(s):  
V Fuster ◽  
M K Dewanjee ◽  
M P Kaye ◽  
D N Fass ◽  
J G White ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Carotid Arteries ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Platelet Deposition ◽  
Wall Interaction ◽  
Scanning Electron

Platelet-arterial wall interaction appears to be important in the genesis of atherosclerosis. Pigs with homozygous von Willebrand’s disease (vWd) appear resistant to atherosclerosis. We investigated whether there is impairment in platelet-arterial wall interaction in porcine vWd. Superficial endothelial injury was produced in a 4 cm segment of carotid artery by drying for 3 minutes in a stream of air which entered one end (100 ml/min) and exited through a small hole in the other end. This procedure was performed in 9 normal and 6 vWd pigs 24 hours after the I.V. infusion of III-Indium-labeled platelets. Carotid blood flow was re-established and the pigs were sacrificed 24 hours later and the carotids fixed in glutaraldehyde.The ratio of radioactivity (cpm/g) of injured/noninjured carotid arteries was markedly decreased in the vWd pigs. In addition, transmission and scanning electron microscopy confirmed superficial endothelial damage in all injured segments, but only significant platelet deposition in the normal pig injured segments.After a mild endothelial injury, this “in vivo” evidence of impaired platelet-arterial wall interaction in vWd may be related to the resistance to atherosclerosis in these animals.

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.

COVID-19 AND STROKE: POSSIBLE CAUSES AND PATHOGENESIS (REVIEW)

Vestnik ◽  
2021 ◽  
pp. 103-106
Author(s):  
А.Е. Кожашева ◽  
С.О. Белесбек ◽  
Д.Ж. Абдимитова ◽  
Б.М. Сакен ◽  
А.П. Бориходжаева ◽  
...  
Keyword(s):  
Preventive Measures ◽  
Cerebrovascular Disorders ◽  
Endothelial Damage ◽  
Cytokine Release ◽  
Contributing Factors ◽  
Acute Cerebrovascular Accident ◽  
Von Willebrand ◽  
The Relationship ◽  
Willebrand Factor ◽  
D Dimer

Появляются доказательства того, что COVID-19 может вызывать выброс цитокинов, состояние гиперкоагуляции и повреждение эндотелия, которое может привести к острому нарушению мозгового кровообращения (ОНМК). В данной статье авторы обсуждают взаимосвязь между COVID-19 и ОНМК, и о возможных факторах, способствующих возникновению инсульта. Как свидетельствует увеличение D-димера, фибриногена, фактора VIII и фактора фон Виллебранда, инфекция SARS-CoV-2 вызывает коагулопатию, нарушает функцию эндотелия и способствует состоянию гиперкоагуляции. В совокупности это предрасполагает пациентов к цереброваскулярным нарушениям. Механизм, лежащий в основе COVID-19 и инсульта, требует дальнейшего изучения, равно как и разработка эффективных терапевтических или профилактических мер. Evidence is emerging that COVID-19 can cause cytokine release, hypercoagulable states, and endothelial damage that can lead to acute cerebrovascular accident (ACVI). In this article, the authors discuss the relationship between COVID-19 and stroke and the possible contributing factors to stroke. As evidenced by an increase in D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection causes coagulopathy, disrupts endothelial function and hypercoagulability. Collectively, this predisposes patients to cerebrovascular disorders. The mechanism underlying COVID-19 and stroke requires further study, as does the development of effective therapeutic or preventive measures.

Plasma von Willebrand factor, thrombosis, and the endothelium: The first 30 years

2006 ◽  
Vol 95 (01) ◽  
pp. 49-55 ◽  
Author(s):  
Andrew Blann
Keyword(s):  
Arterial Disease ◽  
Endothelial Damage ◽  
Contributory Factor ◽  
Long Term Follow Up ◽  
Von Willebrand ◽  
Plasma Marker ◽  
Willebrand Factor ◽  
Late Stages

Summary “It is quite useless to argue the questions concerning the development of intimal scleroses if we study and discuss the late stages of the disease alone. If we wish to gain insight into the complex question of arterio-sclerosis we must attempt to follow the lesion from its earliest beginning” (Klotz and Manning, J Path Bact 1911: 16; 211–20).Over thirty years ago Boneu and colleagues publisheda report of raised levels of plasma vonWillebrand factor (vWf) in patients with arteritis, diabetes and sepsis. They concluded that raised levels of this molecule indicate endothelial damage, and may possibly be a contributory factor in thrombosis in arterial disease. The former aspect of this conclusion is now accepted, and numerous studies on the risk factors for atherosclerosis provide mechanisms for this damage. Other studies have demonstrated raised levels in cancer and in connective tissue disease. Numerous long-term follow-up studies have also demonstrated that increased vWf predicts major cardiovascular end points. However, the link between these studies, and the latter aspect of Boneu’s conclusion, that raised vWf contributes to thrombosis is,although attractive, nevertheless unproven. Despite this, vWf remains the most important plasma marker of endothelial damage/dysfunction and as such attracts clinical attention.

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