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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of sex hormones in atherogenesis has not been well defined. Since hemodialysis patients show signs of feminization and an increased propensity for atherosclerosis they are particularly suited to probe the relationship between estrogen, testosterone, and atherosclerosis. Therefore, we measured plasma total, free, and protein-bound estradiol (E2), testosterone (Te), and prolactin in 28 hemodialysis patients and in 30 age-matched controls. Von Willebrand factor (vWF) levels were also assayed. Total and free E2 as well as Te were significantly decreased in the patients (p less than 0.001). However, the E2/Te ratio was elevated in the patients (p = 0.05), as was vWF (p less than 0.01). No correlations were found between hormone levels and vWF, gynecomastia or vascular disease, but vWF and vascular disease were highly correlated. We conclude that in hemodialysis patients absolute estrogen levels are lower than normal, but that the estrogen/androgen ratio is shifted in favor of estrogen because of the coexistence of androgen deficiency. These findings suggest that an elevation in the estrogen/androgen ratio, rather than an increase in estrogen per se, may be a risk factor for atherosclerosis.
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PMID:Plasma estrogens, androgens, and von Willebrand factor in men on chronic hemodialysis. 326 48

The development of coronary atherosclerosis in response to acute intimal injury and severe hypercholesterolemia was studied in 18 swine, nine normal and nine with von Willebrand's disease, an inherited disorder affecting platelet-vessel wall interactions. The left anterior descending coronary artery was denuded of endothelium by balloon catheterization, while the circumflex and right coronary arteries served as nonballooned controls. All swine were maintained on a 2% cholesterol diet for 4 months. The extent of atherosclerotic involvement was evaluated from four indices: percent intimal area, percent luminal narrowing, ratio of intimal to medial area, and luminal form. No differences in coronary atherosclerosis were observed between phenotypes in either ballooned or nonballooned vessels, nor were there any differences between ballooned and nonballooned vessels within either phenotype (p greater than 0.05). The major variable affecting coronary atherosclerosis was serum cholesterol. There was a significant positive relationship between serum cholesterol concentration and the extent of intimal lesions (r = 0.62, p = 0.006) that was independent of plasma von Willebrand factor concentration. These findings suggest that severe hypercholesterolemia promotes the development of porcine coronary atherosclerosis through a mechanism(s) that is independent of acute intimal injury or von Willebrand factor-mediated platelet response to injury.
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PMID:Development of coronary atherosclerosis in swine with severe hypercholesterolemia. Lack of influence of von Willebrand factor or acute intimal injury. 348 23

We have observed that pigs with impaired platelet function in the form of severe von Willebrand's disease (vWd) are resistant to spontaneous and to diet-induced aortic atherosclerosis. However, it has been reported that vWd pigs are susceptible to coronary atherosclerosis produced by balloon-induced injury of coronary arteries combined with an atherogenic diet. We have evaluated the development of coronary atherosclerosis in normal control (NC) and homozygous vWd pigs in two prospective studies: 1) as a spontaneous process in five NC and vWd pigs receiving a regular diet from the age of 3 months to 4 years; and 2) in nine NC and five vWd receiving a high-fat and high-cholesterol (2%) diet from the age of 3 to 9 months. All of the coronary arteries were analyzed postmortem in 5-mm sections. None of the NC nor the vWd pigs in the spontaneous study showed coronary atherosclerosis or myocardial lesions. In the study of diet-induced atherosclerosis, only one NC and one vWd pig had discrete stenoses; the stenoses affected the three coronary arteries and were significant (50% to 80%) in the NC and mild (greater than 25%) in the vWd pigs; no pigs showed myocardial lesions. Pigs with vWd are resistant to atherosclerosis of the aorta. To assess the resistance or susceptibility to coronary disease in these pigs, a longer follow-up study would be necessary.
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PMID:Spontaneous and diet-induced coronary atherosclerosis in normal swine and swine with von Willebrand disease. 387 27

We have reported that pigs with severe homozygous von Willebrand disease (vWd) are resistant to spontaneous and high fat, high cholesterol, diet-induced atherosclerosis. In this study we report the quantitation of aortic atherosclerotic plaques in three groups of pigs fed with a high fat, high cholesterol (2%) diet from age 3 to 9 months. Nine normal pigs (normal factor VIII antigen, VIII R:AG, and ristocetin co-factor, VIII:RWF) had a mean of 21% atherosclerotic involvement of the distal aortic surface and a 4.5% mean involvement of the entire aorta. Five homozygous vWd pigs (undetected VIII R:AG and VIII:RWF) had a mean of 4.2% atherosclerotic involvement of the distal aortic surface and 1.2% involvement of the entire aorta (p less than 0.01, rank sum test). Five heterozygous vWd pigs (approximately 35% VIII R:AG and VIII:RWF) had a mean of 25% atherosclerotic involvement of the distal aortic surface and 6% involvement of the entire aorta; the results were not significantly different from those in the normal pigs. We concluded that resistance to atherosclerosis is not found in animals with moderate reduction of VIII R:AG and VIII:RWF. This may have implications for humans, since in human vWd both factors are almost always present.
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PMID:Aortic atherosclerosis in pigs with heterozygous von Willebrand disease. Comparison with homozygous von Willebrand and normal pigs. 387 19

Von Willebrand pigs have all the manifestations of the severe human disease. The role of Willebrand antigen (VIII R:AG) and ristocetin cofactor (VIII: RWF) was assessed in these pigs by (1) transfusion and (2) "in vitro" bleeding time assay. The skin bleeding time became normal when the level of transfused Willebrand factor (VIII R:AG/RWF) was raised in the plasma above 30 U/dl. After single or repeated transfusions, skin capillary endothelium and platelets were still distinguished from normal by VIII R:AG deficiency. When incisions in excised porcine skin ("in vitro" bleeding time) were perfused with blood and plasma fractions, haemostasis occurred when plasmatic Willebrand factor exceeded 30 U/dl whether the skin or platelets came from normal or from von Willebrand pigs. The platelet plug occluding the skin incision contained VIII R:AG by immunofluorescence. Willebrand factor appears to coat surfaces and to serve as a platelet attachment protein. These bleeder pigs are resistant to atherosclerosis. If platelets are involved in early atherosclerotic lesions, the role of Willebrand factor in platelet - blood vessel interaction may be important.
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PMID:The role of Willebrand factor in platelet - blood vessel interaction, including a discussion of resistance to atherosclerosis in pigs with von Willebrand's disease. 611 90

The prevalence of von Willebrand's disease (VWD) in Western European countries and Israel was assessed. Possible patients were identified initially by questionnaire and those with plasma levels of von Willebrand factor antigen ( WFAg ; factor VIII related antigen) less than 1 u/dl (less than 1%) were confirmed by immunoradiometric assay performed at four reference centres. The prevalences of severe VWD in Scandinavian countries were similar to each other and about 10 times greater than those in other Western European countries. The prevalence in Israel was intermediate. The Registry will form the basis for future non- invasive epidemiological studies of atherosclerosis in these individuals.
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PMID:Atherosclerosis and von Willebrand factor. I. Prevalence of severe von Willebrand's disease in western Europe and Israel. 660 12

The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis developed to a similar degree in all three phenotypic groups. The mean intimal thickness at the site of maximal thickness in ballooned vessels was .51 mm in the normal pigs, .67 mm in carrier pigs, and .55 mm in bleeder pigs. The intimal thickness of non-ballooned vessels was .28 mm in normal pigs, .28 mm in carrier pigs, and .35 mm in bleeder pigs. Fibrous lesions of atherosclerosis covered an average of 3.88% of the aorta in normal pigs, 2.83% in carrier pigs, and 2.37% in bleeder pigs. The difference between the aortic lesions of normal animals and bleeders was significant (P less than .05). Absence of von Willebrand factor was associated with limited resistance to atherosclerosis in the aortas of experimental pigs but did not affect the development of atherosclerosis in either ballooned or nonballooned coronary arteries. These findings suggest, first, that von Willebrand factor function is not essential to the development of the atherosclerotic lesion in this model and, second, that the role of the von Willebrand factor in the development of atherosclerosis is complicated and appears to involve interaction with variables not yet defined.
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PMID:Susceptibility to atherosclerosis in aortas and coronary arteries of swine with von Willebrand's disease. 697 May 27

A platelet derived growth factor released following platelet adhesion to the subendothelium of damaged arteries may promote the development of atherosclerotic lesions. Consequently patients with von Willebrand's disease in whom platelet adhesion is abnormal may be protected from atherosclerosis. This possibility was investigated by performing an autopsy study on an elderly patient who had suffered from severe von Willebrand's disease. Extensive atherosclerotic lesions were found at post mortem suggesting that platelets may not play a clinically significant role in the causation of atherosclerosis.
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PMID:Autopsy findings in an elderly man suffering from severe von Willebrand's disease. 697 99

The extent of coronary and aortic atherosclerosis was examined in pigs following balloon-catheter injury of coronary arteries and subsequent feeding of an atherogenic diet for 4 months. The pigs were either exposed intermittently to 100 ppm carbon monoxide or to ambient air alone. Three types of pigs were used: normals, homozygotes for von Willebrand's disease (bleeders), and heterozygotes (carriers). The 3 types of pigs developed coronary artery intimal lesions of similar thickness. Aortic lesions, quantified as percent of aortic surface involved with sudanophilia and raised fibrous plaques, were slightly less extensive in bleeder pigs than in normals. Carbon monoxide exposure did not increase the thickness of coronary artery intimal lesions, nor did it increase the percent of aortic surface involved with sudanophilia or raised fibrous lesions. These results suggest that exposure to low levels of carbon monoxide does not perceptibly enhance atherogenesis induced by hypercholesterolemia. None of 14 bleeder pigs showed evidence of myocardial infarction, despite significant coronary artery narrowing. Of the 24 normal and carrier pigs, 5 showed myocardial infarction. Four of these 5 pigs were exposed to carbon monoxide, while 1 was not exposed. These findings suggest that exposure to low levels of carbon monoxide may increase the incidence of myocardial infarction and that the absence of von Willebrand factor may be protective.
Atherosclerosis 1982 Jun
PMID:Effect of carbon monoxide on atherogenesis in normal pigs and pigs with von Willebrand's disease. 698 17

Hemostatic factors play a crucial role in generating the occlusive thrombotic plug at sites of vascular damage (atherothrombosis). It remains uncertain, however, whether hemostatic factors contribute directly or indirectly to the pathogenesis of atherosclerosis. For example, 'hypercoagulable states' (eg, antithrombin deficiency, Factor VLeiden) generally predispose to venous thrombotic events, but not atherosclerosis. Further, 'hemophilic states' (eg, factor VIII deficiency, von Willebrand's disease) do not protect against atherosclerosis. Nevertheless, research has been stimulated by several clinical studies showing that an elevated fibrinogen level is a strong and independent risk factor for cardiovascular (arterial) thrombotic events. Moreover, basic investigations have demonstrated fibrin(ogen) antigens in evolving atherosclerotic plaques, and have suggested a smooth muscle mitogenic effect of fibrin. Other factors that may contribute to atherogenesis include platelets and platelet-derived microparticles, coagulation factor VII and lipoprotein (a) [Lp(a)]. Lp(a) is of particular interest since elevated levels of this lipoprotein particle are strongly linked to cardiovascular disease. Lp(a) appears to inhibit natural fibrinolysis, suggesting that this factor could represent an important link between thrombotic and lipid atherogenic mechanisms. Further work defining a role for the hemostatic system in atherogenesis is important because of the potential benefit of pharmacological manipulation of hemostatic risk factors, such as agents that lower fibrinogen levels.
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PMID:Hemostasis and atherosclerosis. 775 46


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