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

Hypercholesterolemia (HC = hypercholesterolemia or hypercholesterolemic) was produced in rabbits by feeding them diets supplemented with cholesterol and peanut oil. Platelet counts and volumes, white cell counts, reticulocyte counts, and hematocrits were determined at intervals for 8-12 weeks in blood from HC animals and controls on a normal rabbit diet. Microthrombocytosis was a consistent occurrence in the presence of HC, developing as early as 2 weeks into the diet. Microthrombocytosis was generally associated with normal platelet counts, but mild thrombocytosis occurred late in the diet at the time of the highest levels of serum cholesterol (greater than 1300 mg/dl). Platelets from HC rabbits were morphologically normal by transmission electron microscopy. Survivals of 51Cr-labeled platelets from HC and non-HC rabbits were measured in HC and non-HC recipients. The results identified an intrinsic defect in the ability of HC platelets to survive in the circulation. They also confirmed previous findings of an environmental defect in HC that causes shortened platelet survival.
Atherosclerosis 1988 Nov
PMID:Morphological and kinetic abnormalities of platelets in hypercholesterolemic rabbits. 321 78

To investigate changes in platelet function, count and metabolism following fish intake among Japanese, we conducted an experimental intervention study of seven healthy Japanese volunteers (4 males and 3 females) aged 28-58 years. We supplemented their diets with an approximate daily intake of 200-400 g fish which is equivalent to about 10 g n3-polyunsaturated fatty acids (about 3.5 g eicosapentaenoic acid plus 5.0 g docosahexaenoic acid) during the 17 days. The study continued until the 23rd day after returning to an ad libitum diet. The proportion of serum n3-polyunsaturated fatty acids increased two-fold on 5th day and three-fold on 15th day of fish supplementation, but decreased to one and a half-fold on the 2nd day and returned to the level before fish supplementation on the 12th day after returning to an ad libitum diet. The proportion of serum n6-polyunsaturated fatty acids decreased by 17% to the level before fish supplementation on the 5th day, 33% on the 15th day of fish supplementation. However, the decrease was only 10% on the 2nd day and the proportion returned to the same level as before fish supplementation on the 12th day after returning to an ad libitum diet. As a result, the serum n3/n6 polyunsaturated fatty acid ratio increased four-fold on the 15th day of fish supplementation, and returned to the baseline level on the 12th day after returning to an ad libitum diet. Platelet counts decreased and the mean platelet volume increased during fish supplementation. Both parameters returned to the level before fish supplementation on the 12th day after returning to an ad libitum diet. The counts and proportion of large type platelets increased significantly during fish supplementation. Although platelet aggregation by ADP (adenosine 5'-diphosphate) did not change significantly, platelet aggregation by collagen tended to decrease during fish supplementation. Platelet factor 4, one of the indices of platelet activity, decreased significantly during fish supplementation. The mean serum triglyceride level declined during fish supplementation, but returned to the level just before fish supplementation on the 2nd day after returning to an ad libitum diet. The mean plasma fibrinogen level tended to decline during fish supplementation and remained lower until the 12th day after returning to an ad libitum diet. Habitual fish intake may attenuate the development of atherosclerosis and prevent ischemic heart disease through suppression of platelet activity, and by reducing platelet counts and serum triglyceride levels.
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PMID:[The effects of fish supplementation of platelet function, count and metabolism in healthy Japanese]. 1019 17

Thrombosis is a complication of atherosclerosis and monocytes play a determinant role either in the progression of atherosclerotic plaque or in blood coagulation by way of tissue factor expression. Platelets play a direct role in thrombosis and a hyperfunctional state has been described in hypercholesterolemic subjects. Moreover, platelets seem to be able to enhance monocyte activity. Cholesterol-lowering molecules (statins) are reported to reduce cardiovascular risk, either by decreasing the circulating level of cholesterol or by non-lipidic actions such as the reduction of monocyte and platelet activity. The aim of our study was to investigate the influence of platelets on the expression of tissue factor by monocytes and the effect induced by cerivastatin. We measured tissue factor levels by ELISA and the procoagulant activity of stimulated monocytes by a clotting assay on cellular preparations and whole blood in 40 hypercholesterolemic subjects (22 male, 18 female, mean age 52.7 +/- 12 years, total cholesterol 251.6 +/- 19.9 mg/dl) before and after cerivastatin addition. Tissue factor expression was enhanced in hypercholesterolemic subjects compared with normal subjects (31.6 +/- 7.6 vs. 23 +/- 5.8 pg/cells, P < 0.01). The presence of platelets increased the amount of tissue factor (55.3 +/- 7.3 pg/cells, P < 0.001) and cerivastatin reduced the expression of tissue factor in isolated monocytes, in the mixed cellular system, and in whole blood (19.6 +/- 4.1 pg/cells, P < 0.001). In conclusion, tissue factor expression by monocytes is enhanced in hypercholesterolemic subjects compared with normal controls. Platelets enhance monocyte production of tissue factor, and cerivastatin is able to counteract this prothrombotic mechanism.
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PMID:Role of platelets in tissue factor expression by monocytes in normal and hypercholesterolemic subjects. In vitro effect of cerivastatin. 1119 73

Microalbuminuria is more prevalent in patients with risk factors for cardiovascular diseases and reflects the widespread vascular damage predisposing to atherosclerosis. It is also found in acute clinical conditions, e.g. myocardial infarction, pancreatitis and stroke, and predicts poor outcome. The mechanism leading to increased albuminuria in these conditions is unknown, therefore we designed the study to investigate the relationship between increased urinary albumin excretion in acute stroke and biochemical markers of stress and inflammatory reaction as well as markers of endothelial damage. Sixty patients with first-time ischemic stroke, admitted within 24 hours to the stroke unit took part in the study. We excluded patients with diabetes, infection, nephropathy and abnormal urinalysis. Neurological deficit was assessed on admission and after 24 hours by Scandinavian Stroke Scale. Daily urinary albumin excretion on Day 2 was measured using the immunonephelometric method. The serum cortisol concentration was measured on Day 1 at 6.00 AM, 10.00 AM, 6.00 PM and 10.00 PM. Daily urinary excretion of epinephrine and norepinephrine was measured on Day 1 and on Day 3. We assessed also hematocrit, ESR, serum glucose and fibrinogen, leukocytosis, thrombocytosis and von Willebrand factor activity. Microalbuminuria was found in 46.7% of patients. There was no difference between patients with micro-albuminuria and those without it regarding sex, age and the prevalence of risk factors for stroke. Patients with micro-albuminuria had greater urinary excretion of epinephrine on Day 1. We did not find any differences regarding von Willebrand factor activity, serum cortisol concentration or other assessed variables. In logistic regression analysis the urinary excretion of epinephrine on Day 1 was the only independent variable predicting the occurrence of microalbuminuria in patients with acute ischemic stroke.
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PMID:[Mechanisms determining the occurrence of microalbuminuria in patients with acute ischemic stroke]. 1195 14

We studied whether circulating activated platelets and platelet-leukocyte aggregates cause the development of atherosclerotic lesions in apolipoprotein-E-deficient (Apoe(-/-)) mice. Circulating activated platelets bound to leukocytes, preferentially monocytes, to form platelet-monocyte/leukocyte aggregates. Activated platelets and platelet-leukocyte aggregates interacted with atherosclerotic lesions. The interactions of activated platelets with monocytes and atherosclerotic arteries led to delivery of the platelet-derived chemokines CCL5 (regulated on activation, normal T cell expressed and secreted, RANTES) and CXCL4 (platelet factor 4) to the monocyte surface and endothelium of atherosclerotic arteries. The presence of activated platelets promoted leukocyte binding of vascular cell adhesion molecule-1 (VCAM-1) and increased their adhesiveness to inflamed or atherosclerotic endothelium. Injection of activated wild-type, but not P-selectin-deficient, platelets increased monocyte arrest on the surface of atherosclerotic lesions and the size of atherosclerotic lesions in Apoe(-/-) mice. Our results indicate that circulating activated platelets and platelet-leukocyte/monocyte aggregates promote formation of atherosclerotic lesions. This role of activated platelets in atherosclerosis is attributed to platelet P-selectin-mediated delivery of platelet-derived proinflammatory factors to monocytes/leukocytes and the vessel wall.
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PMID:Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. 1248 7

Acute leukemias with thrombocytosis have been recently linked with structural abnormalities of the short arm of chromosome 3. A 46-year-old man with a 2-month history of recurrent transient ischemic attacks and abdominal pain developed an ischemic left foot and a gangrenous toe as his initial symptoms. Platelet count was 3.5 x 10(6)/microL, and despite plateletpheresis, the patient required left-leg amputation. Pathologic examination was remarkable for arterial thrombosis in the absence of atherosclerotic lesions. A diagnosis of acute myeloid leukemia with a novel translocation between chromosomes 3q21, 16, and 7 was made. Induction therapy was unsuccessful, and the patient died of overwhelming sepsis within 5 weeks of diagnosis. The striking features of this case were extreme symptomatic thrombocytosis, peripheral gangrene without atherosclerosis, and a novel three-way chromosomal translocation involving chromosome 3q21.
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PMID:Acute myelogenous leukemia associated with extreme symptomatic thrombocytosis and chromosome 3q translocation: case report and review of literature. 1250 63

Thrombopoietin (TPO) is the major regulator of platelet production. Plasma levels of TPO are thought to be regulated by its binding to platelets and megakaryocytes. Here we have used a model of cardiac surgery with cardiopulmonary bypass (CBP) to test the possibility that changes in TPO levels are influenced by the presence of coronary artery disease (CAD) and by changes in interleukin-6 (IL-6). After surgery patients with CAD (n = 22) or with normal coronary arteries (n = 11) showed a significant thrombocytopaenia followed by a reactive thrombocytosis. The platelet recovery was preceded by a significant rise in TPO (from 62.6 +/- 9.4 pg/ml at baseline to 129.2 +/- 19 pg/ml at 60 h, P <0.001), which in turn was preceded by, and was positively correlated with, a marked increase in circulating IL-6 (from 1.5 +/- 0.3 pg/ml at baseline to 269.3 +/- 30.6 pg/ml at 3-12 h, P <0.001). The rise of both IL-6 and TPO was significantly larger in patients with CAD. No correlation was found between the post-operative drop in platelet mass and changes in either the TPO or IL-6 levels. These findings suggest that in man circulating TPO levels, besides being controlled by changes in platelet mass, are influenced by inflammatory processes, including the presence of coronary atherosclerosis.
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PMID:Rise of circulating thrombopoietin following cardiothoracic surgery is potentiated in patients with coronary atherosclerosis: correlation with a preceding increase in levels of interleukin-6. 1262 39

Oxidatively-modified fibrinogen induces platelet aggregation and potentiates ADP-induced platelet aggregation and production of active oxygen forms in zymosan-stimulated leukocytes. Fibrinogen induces IL-8 production in primary culture of endothelial cells from human umbilical vein; the oxidized form of fibrinogen is more active, similarly as during induction of the expression cell adhesion molecules (P-selectin and ICAM-1). Oxidized fibrinogen (10 and 20% oxidation degree) impairs microrheological properties of the blood, sharply reduces erythrocyte deformability, modifies blood viscosity, and reduces suspension stability of the blood. Oxidized fibrinogen modified blood clotting parameters and ADP-, ristocetin-, and collagen-induced platelet aggregation in whole blood. Oxidized fibrinogen disordered the formation of fibrin clot and blood clotting process. Platelet aggregation was activated in response to ADP, but not to ristocetin and collagen, the degree of activation increased in direct proportion to the degree of fibrinogen oxidation. This indicates the "dysregulatory" effect of oxidized fibrinogen on platelets. The formation of platelet complexes with polymorphonuclear leukocytes was intensified in the presence of oxidized fibrinogen; polymorphonuclear leukocyte luminol-dependent fluorescence intensity in the presence of platelets increased after incubation with oxidized fibrinogen in comparison with native fibrinogen. Hence, oxidized fibrinogen plays an important role in the development of atherosclerosis and its complications (thromboses).
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PMID:Effects of oxidized fibrinogen on the functions of blood cells, blood clotting, and rheology. 1845 45

Patients with reactive thrombocytosis are generally asymptomatic and platelet counts of up to 1,000,000/microL are seen in this disorder. However, in a small proportion of cases platelet counts may be in the range generally seen in Clonal Thrombocytosis (CT). In elderly patients or those with symptomatic atherosclerosis or thrombotic disease or immobility, thrombosis may occur even with reactive thrombocytosis. We report a case of a rare presentation of Reactive Thrombocytosis with digital gangrene in an elderly lady. She was evaluated for thrombocytosis and was given supportive treatment after which she clinically improved.
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PMID:Reactive thrombocytosis with digital gangrene. 1915 29

Increasing evidence demonstrates that interleukin (IL)-32 is a pro-inflammatory cytokine, inducing IL-1alpha, IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and chemokines via nuclear factor (NF)-kappaB, p38 mitogen-activated protein kinase (MAPK), and activating protein (AP)-1 activation. Here we report that IL-32 is expressed and is also functional in human vascular endothelial cells (EC) of various origins. Compared with primary blood monocytes, high levels of IL-32 are constitutively produced in human umbilical vein EC (HUVEC), aortic macrovascular EC, and cardiac as well as pulmonary microvascular EC. At concentrations as low as 0.1 ng/ml, IL-1beta stimulated IL-32 up to 15-fold over constitutive levels, whereas 10 ng/ml of TNFalpha or 100 ng/ml of lipopolysaccharide (LPS) were required to induce similar quantities of IL-32. IL-1beta-induced IL-32 was reduced by inhibition of the IkappaB kinase-beta/NF-kappaB and ERK pathways. In addition to IL-1beta, pro-coagulant concentrations of thrombin or fresh platelets increased IL-32 protein up to 6-fold. IL-1beta and thrombin induced an isoform-switch in steady-state mRNA levels from IL-32alpha/gamma to beta/epsilon. Adult EC responded in a similar fashion. To prove functionality, we silenced endogenous IL-32 with siRNA, decreasing intracellular IL-32 protein levels by 86%. The knockdown of IL-32 resulted in reduction of constitutive as well as IL-1beta-induced intercellular adhesion molecule-1 (ICAM-1) (of 55% and 54%, respectively), IL-1alpha (of 62% and 43%), IL-6 (of 53% and 43%), and IL-8 (of 46% and 42%). In contrast, the anti-inflammatory/anti-coagulant CD141/thrombomodulin increased markedly when IL-32 was silenced. This study introduces IL-32 as a critical regulator of endothelial function, expanding the properties of this cytokine relevant to coagulation, endothelial inflammation, and atherosclerosis.
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PMID:IL-32-dependent effects of IL-1beta on endothelial cell functions. 1922 41


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