Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is experimental evidence that platelets, by interacting with the arterial wall may be important in the initiation of atherosclerosis. This paper describes the results of consecutive experiments indicating that pigs with impaired platelet-blood vessel interaction in the form of von Willebrand's disease are resistant to the development of atherosclerotic plaques. Ongoing experiments in these pigs are providing significant insight into the relationship of the circulating platelets, the endothelial cell and circulating von Willebrand factor, and the reactivity of the arterial wall in the process of atherosclerosis.
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PMID:Von Willebrand's disease in pigs and atherosclerosis. 39 4

Seventeen patients had spontaneous orbital hemorrhages. The usual symptoms were acute onset of pain, proptosis, and vomiting with decreased vision, limitation of motility, and ecchymosis of the eyelids occurring in some patients. The children often developed a progressive space occupying lesion that simulated a neoplasm. Most patients had underlying venous anomalies, although several elderly patients with atherosclerosis developed arterial hemorrhages with more abrupt and dramatic symptoms. Other associated conditions included hypertension, anemia, labor, and von Willebrand's disease. The visual outcome was good except in the elderly patients, half of whom had severe and permanent visual loss.
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PMID:Orbital hemorrhage. 47 97

This editorial discusses 3 points of evidence which implicate that oral contraceptives induce characteristic morphological changes in platelets. These morphological alterations were reported after routine examination of blood smears of oral contraceptive users, and speculation exists that oral contraceptives may affect the membrane of the erythrocyte or the stability of platelet granules. The need for a test to determine at-risk patients for thromboembolic consequences upon initiation of oral contraceptive therapy is expressed; it may involve studying atherosclerosis and its method of development. Von Willebrand disease, or angiohemophilia, in swine completely protects the animals against spontaneous or diet-induced atherosclerosis; hence, the induction of this disease as a model for studying platelet and coagulation functions in humans might be tenable. Presently, there is no means of inducting von Willebrand disease; however, evidence on the preventability of atherosclerosis could be gleaned from controlled, long-term trials of anticoagulants and platelet inhibitors in coronary by-pass graft recipients.
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PMID:Platelets, thrombosis, coagulation, and atherosclerosis. 88 66

The relationship of apolipoprotein-B genotype (Lpb) to diet-induced hypercholesterolemia and atherosclerosis was studied in von Willebrand disease (vWD) and normal pigs. Von Willebrand and normal pigs developed comparable levels of hypercholesterolemia (respectively, 757.9 +/- 49.4 versus 772.8 +/- 47.9 mg/dl, P = 0.95). Pigs with Lpb1/5 and Lpb5/8 genotypes, however, developed significantly higher serum cholesterol levels than those with other Lpb genotypes (866.1 +/- 64.0 mg/dl, P = 0.0343). Coronary and aortic atherosclerosis, measured by computer-assisted automated image analyzer, were not significantly different between vWD and normal pigs. Pigs with an Lpb5 allele developed significantly more atherosclerosis than those with the Lpb3/8 or Lpb8/8 genotypes or the rare Lpb1 allele (r greater than or equal to 0.434, P less than or equal to 0.05). Polymorphism in apolipoprotein B100 genotype, then, significantly influenced the severity of diet-induced hypercholesterolemia and atherosclerotic plaque formation in vWD and normal swine without regard to the vWD genotype.
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PMID:Porcine von Willebrand disease and atherosclerosis. Influence of polymorphism in apolipoprotein B100 genotype. 173 33

With normal and von Willebrand disease (vWD) pigs, we studied the role of von Willebrand factor (vWF) in platelet-vessel wall interactions and occlusive arterial thrombosis. Two methods of arterial injury have been used to determine the thrombotic response of flowing blood in vivo. The first involves balloon catheter injury. After superficial denudation of endothelium from coronary intima, platelets adhere to the subendothelium in a monolayer. Similar numbers of adherent platelets are found in both phenotypes, but platelets in vWD pigs have impaired pseudopod formation and are less well spread morphological indexes of limited platelet activation. Deeper injury, which involves the media, produces nonocclusive platelet-fibrin microthrombi. The second injury method involves pinching the artery at a site of superimposed stenosis, a procedure that almost always exposes media. This procedure induces platelet-fibrin microthrombi in normal and vWD pigs, but only normal pigs develop occlusive thrombosis. Both methods of arterial injury have also been performed in normal and vWD pigs with diet-induced hypercholesterolemia and atherosclerosis. Atherosclerosis promotes platelet spread in vWD pigs but does not abolish the protection from stenosis and injury-induced occlusive thrombosis. In addition, neutralization of vWF activity in normal pigs by a monoclonal antibody prevents the induction of occlusive thrombosis by the stenosis and pinch-injury procedure. This monoclonal antibody also causes performed platelet aggregates to break up. These experimental models of inducing arterial thrombosis have been used in normal and vWD pigs to demonstrate interactions between normal and atherosclerotic vessel wall constituents, circulating platelets and vWF that are fundamental in the process of arterial thrombosis.
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PMID:Role of von Willebrand factor in arterial thrombosis. Studies in normal and von Willebrand disease pigs. 204 72

The physiologic mechanisms that influence plasma levels of von Willebrand factor (vWF) are poorly understood but include race, blood group, age, pregnancy, exercise, and adrenergic and neurohumoral stimuli. Inherited abnormalities in von Willebrand's disease (vWD) are associated with a defect of the vWF gene on chromosome 12, but in some cases, coexistence of impaired response of plasminogen activator and telangiectasia suggests the presence of a regulatory defect or more extensive endothelial perturbation. Three broad types of vWD are recognized; in addition, a platelet-type vWD (pseudo-vWD) is due to an abnormal platelet receptor for vWF. The prevalence of vWD, which is difficult to determine because of variations in severity even within a kindred, is reportedly as high as 1%. In a survey of European patients, the prevalence of treated vWD varied from 4.5 to 24 per million. Preliminary results of an international survey of vWD indicate that about 3% of treated patients have seroconversion to human immunodeficiency virus, 50% of whom have symptoms. Inhibitor of vWF occurs in type III vWD after treatment and is associated with the presence of gene deletions. Acquired vWD may complicate lymphoproliferative and autoimmune disorders, and proteolytic degradation of vWF complicates myeloproliferative disorders. The level of vWF is increased during pregnancy and in vascular and other disorders; it may be involved in the pathogenesis of atherosclerosis. High-molecular-weight multimers of vWF and a cofactor are thought to promote the formation of microthrombi in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Thus, study of vWD has shed light on pathogenetic mechanisms in a wide range of disorders.
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PMID:von Willebrand factor: clinical features of inherited and acquired disorders. 207 62

The thrombotic response of atherosclerotic arteries to stenosis and injury was studied in 14 pigs, eight normal and six with von Willebrand's disease (vWD). Atherosclerosis was produced by feeding a 1% to 2% cholesterol diet for 24 weeks. Both groups of pigs developed severe hypercholesterolemia, greater than five times baseline values. Coronary atherosclerosis was detected in all vWD pigs and in all but one normal pig and was not significantly different between groups. At sacrifice under general anesthesia, a Goldblatt clamp (GC) was positioned around the left anterior descending coronary (LAD) and carotid arteries to produce a stenotic segment, which was pinch-injured with needle holders. A 20 MHz Doppler velocity crystal was placed distal to the GC to detect cyclic flow reductions or permanent cessation of flow velocity indicative of occlusive thrombosis. In the phenotypically normal pigs with diet-induced atherosclerosis, occlusive thrombosis was detected in seven of seven LAD and seven of seven carotid arteries. In atherosclerotic vWD pigs, occlusive thrombosis failed to form in six LAD and 10 carotid arteries (p less than 0.003, Wilcoxon rank sum test). Scanning electron micrographs demonstrated platelet-fibrin microthrombi in both groups of pigs; only phenotypically normal pigs had occlusive thrombi. Von Willebrand factor is essential for the development of occlusive thrombosis and appears to support the progression of a mixed microthrombus to an occlusive thrombus.
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PMID:von Willebrand factor and occlusive arterial thrombosis. A study in normal and von Willebrand's disease pigs with diet-induced hypercholesterolemia and atherosclerosis. 234 1

The von Willebrand factor (VWF) is a link in the platelet-vessel wall interaction which plays an essential role in the response of the vessel wall to an atherosclerosis-including aggression. However, can von Willebrand's disease really prevent the development of atherosclerosis? The authors report 3 cases of young men aged 36, 40 and 51 years with atherogenic risk factors and von Willebrand's disease (two mild and one severe form). The three patients developed both atherosclerotic lesions and thrombosis. This would suggest that VWF deficiency does not protect humans from atherosclerosis.
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PMID:[von Willebrand's disease and coronary atherosclerosis. Apropos of 3 cases]. 251 40

A thrombus is an abnormal manifestation of normal haemostasis occurring on the internal surface of the blood vessels. Endothelial injury is the first event which ultimately may result in arterial thrombosis. Platelets stick to subendothelial components, are activated and release a number of mediators which aggregate new platelets. Simultaneously, thrombin is generated on the platelet surface and enhances these phenomenons. Due to the high blood flow which avoids local thrombin accumulation, arterial thrombosis is mainly composed of platelets with a poor fibrin content. A mural arterial thrombosis may embolize, be incorporated in the vessel wall, or occlude the lumen of the artery. Platelets are involved in the development of atherosclerosis: severe thrombocytopenia or von Willebrand disease protect efficiently against experimental atherosclerosis; several clinical conditions known to increase cardiovascular diseases are also associated with an increased platelet aggregability; in contrast, polyunsaturated fatty acids decrease platelets aggregability and protect against vascular diseases.
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PMID:[Role of platelets in atherosclerosis and arterial thrombosis]. 259 16

There is now considerable evidence to suggest that some aspects of early lesion formation and later lesion growth are a reaction to injury. Hemodynamic factors are important in determining the site of injury and may produce injury directly. Injury can lead to atherogenesis in animal models as well as in humans. Superficial injury exposes the subendothelium, allowing platelet adhesion, which at high shear rates is dependent on vWF. Platelet adhesion and degranulation release PDGF, which stimulates smooth muscle cell proliferation, synthetic functions, and vasoconstriction. LDL stimulates smooth muscle cell growth as well as damages endothelium in some experimental systems. Thus, a link is provided between platelet and lipid involvement in atherosclerosis. Direct evidence for a role of platelets in atherogenesis comes from studies in which animals were treated to reduce platelet number or function or in which platelet function is genetically impaired (pigs with von Willebrand's disease). In these models, reduced platelet function is associated with less atherosclerosis. Deeper injury exposes collagen, with subsequent platelet aggregation, thrombin and fibrin generation. The role of reduced production of PGI2 and fibrinolytic agents following severe damage is unknown. Deep injury to the vessel occurs during plaque fissuring, the pathologic process underlying most cases of myocardial infarction, unstable angina, and some cases of sudden death. Angioplasty produces amelioration of many patients' symptoms and is safe. However, acute occlusion occurs occasionally, and restenosis in the first year occurs in some 30 percent of patients treated. Angioplasty damages the arterial wall, with endothelial denudation and intimal and medial splitting. Why does this, and plaque injury, by stimulating platelet deposition, not produce more restenosis? Changes in arterial anatomy are likely to be important: the increase in vessel diameter and in blood flow produce conditions less favorable for thrombotic or arteriosclerotic restenosis.
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PMID:Role of platelets in atherogenesis: relevance to coronary arterial restenosis after angioplasty. 295 94


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