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

Individuals with chronically elevated glucose and/or insulin levels, i.e., most patients with type 2 diabetes, have accelerated atherosclerosis and are prone to acute vascular events. We have tested the hypothesis that hyperglycemia and/or hyperinsulinemia singly or combined may increase tissue factor, the primary initiator of blood coagulation. We have determined changes in circulating tissue factor procoagulant activity (PCA) and other procoagulation proteins in healthy volunteers exposed to 24 h of selective hyperinsulinemia, selective hyperglycemia, or combined hyperinsulinemia and hyperglycemia. Combined elevations of plasma insulin and glucose levels for 24 h produced a ninefold increase in tissue factor PCA, which was associated with an increase in monocyte tissue factor protein (flow cytometry) and mRNA (RT-PCR), increases in plasma thrombin-antithrombin complexes, prothrombin fragment 1.2, factor VIII coagulant activity, and platelet CD40 ligand as well as decreases in factor VIIa, factor VII coagulant activities, and factor VII antigen. Effects of selective hyperinsulinemia and selective hyperglycemia were less striking but appeared to be additive. We conclude that hyperinsulinemia and hyperglycemia but particularly the combination of both create a prothrombotic state and in addition may be proinflammatory and proatherogenic because of the proinflammatory actions of CD40 ligand and tissue factor.
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PMID:Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. 1638 Apr 94

Particulate air pollution is known to increase cardiovascular morbidity and mortality. Proposed mechanisms underlying this increase include effects on inflammation, coagulation factors, and oxidative stress, which could increase the risk of coronary events and atherosclerosis. The aim of this study was to examine whether short-term exposure to wood smoke affects markers of inflammation, blood hemostasis, and lipid peroxidation in healthy humans. Thirteen subjects were exposed to wood smoke and clean air in a chamber during two 4-h sessions, 1 wk apart. The mass concentrations of fine particles at wood smoke exposure were 240-280 mug/m3, and number concentrations were 95,000-180,000/cm3. About half of the particles were ultrafine (< 100 nm). Blood and urine samples were taken before and after the experiment. Exposure to wood smoke increased the levels of serum amyloid A, a cardiovascular risk factor, as well as factor VIII in plasma and the factor VIII/von Willebrand factor ratio, indicating a slight effect on the balance of coagulation factors. Moreover, there was an increased urinary excretion of free 8-iso-prostaglandin2alpha, a major F2-isoprostane, though this was based on nine subjects only, indicating a temporary increase in free radical-mediated lipid peroxidation. Thus, wood-smoke particles at levels that can be found in smoky indoor environments seem to affect inflammation, coagulation, and possibly lipid peroxidation. These factors may be involved in the mechanisms whereby particulate air pollution affects cardiovascular morbidity and mortality. The exposure setup could be used to establish which particle characteristics are critical for the effects.
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PMID:Experimental exposure to wood-smoke particles in healthy humans: effects on markers of inflammation, coagulation, and lipid peroxidation. 1686 2

Oxidatively modified low-density lipoprotein (OxLDL) is present in atherosclerotic lesions and has been proposed to play an important role in atherogenesis. Asp-hemolysin, a hemolytic toxin from Aspergillus fumigatus, is a binding protein for OxLDL. This study was undertaken to clarify the biological activity of OxLDL and the potentially of Asp-hemolysin as a regulation factor to atherogenic effect by OxLDL. We first analyzed the interaction between OxLDL and blood coagulation factors, which are involved in the blood coagulation pathway. OxLDL caused prolongation of activated partial thromboplastin time (APTT) as a parameter of the intrinsic pathway of blood coagulation in a dose- and oxidation time-dependent manner. In addition, OxLDL significantly inhibited blood coagulation factor VIII, IX, and XI activity. Furthermore, we demonstrated that factor VIII binds to OxLDL. These results indicate that the binding of factor VIII to OxLDL affects the intrinsic pathway of the blood coagulation cascade. Next, to clarify the structure-function relationship of Asp-hemolysin, we expressed Asp-hemolysin in Escherichia coli as a fusion protein with a maltose-binding protein (MBP) and purified it by affinity chromatography. The purified recombinant Asp-hemolysin showed an immunoreactivity with the anti-Asp-hemolysin antibody. In addition, MBP-Asp-hemolysin fusion protein exhibited binding activity to Ox-LDL as did native Asp-hemolysin. Furthermore, to investigate the effect of the Asp-hemolysin-related peptide (P-21), a synthetic peptide derived from a region of Asp-hemolysin that is rich in positive charges, on macrophage proliferation induced by OxLDL. P-21 inhibited OxLDL-induced macrophage proliferation in a dose-dependent manner. In addition, the binding analysis of P-21 to OxLDL indicated that P-21 binds to OxLDL. These results indicate that P-21 inhibits the OxLDL-induced macrophage proliferation through binding of P-21 to OxLDL. In conclusion, we have shown that OxLDL affects the intrinsic pathway of blood coagulation, and its mechanism is dependent on the binding of factor VIII to OxLDL. Furthermore, we indicate the possibility that Asp-hemolysin is a useful tool to investigate the pathophysiological significance of OxLDL. In particular, since the P-21, an Asp-hemolysin-related peptide, inhibits the OxLDL-induced macrophage proliferation through binding of P-21 to OxLDL, further study on the binding mechanism between Asp-hemolysin-related peptide and OxLDL may provide important information on the prevention and treatment of atherosclerosis.
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PMID:[Biological activity of Asp-hemolysin as a regulation factor to atherogenic effect by oxidized low-density lipoprotein]. 1701 24

Haemostatic and inflammatory markers have been hypothesised to mediate the relationship of social class and cardiovascular disease (CVD). We investigated whether a range of inflammatory/haemostatic markers are associated with social class independent of chronic diseases and behavioural risk factors in a population-based sample of 2682 British men aged 60-79 without a physician diagnosis of CVD, diabetes or musculoskeletal disease requiring anti-inflammatory medications. Men in lower social classes had higher mean levels of C-reactive protein, fibrinogen, interleukin-6, white blood cell count, von Willebrand factor (vWF), factor VIII, activated protein C (APC) resistance, plasma viscosity, fibrin D-dimer and platelet count, compared to higher social class groups; but not of tissue plasminogen activator antigen, haematocrit or activated partial prothrombin time. After adjustment for behavioural risk factors (smoking, alcohol, physical activity and body mass), the associations of social class with vWF, factor VIII, APC resistance, plasma viscosity, and platelet count though weakened, remained statistically significant, while those of other markers were considerably attenuated. In this study of older men without CVD, the social gradient in inflammatory and haemostatic markers was substantially explained by behavioural risk factors. The effect of socio-economic gradient on the factor VIII-vWF complex, APC resistance, plasma viscosity and platelet count merits further study.
Atherosclerosis 2008 Apr
PMID:Relationships of inflammatory and haemostatic markers with social class: results from a population-based study of older men. 1739 87

In the HIV infection, the short time-scale between the HIV-induced cardiovascular events and the onset of antiretroviral therapy elicits a thrombophilic co-factor that worsens the induced atherosclerosis. We compared the factor VIII plasma activity, previously implicated in arterial and venous thrombosis, with a surrogate marker of atherosclerosis, the carotid intima-media thickness, and with the usual atherosclerosis risk factors in 154 HIV infected outpatients. The FVIII plasma activity is significantly associated with the carotid intima-media thickness and, strongly, with blood glucose and triglycerides levels. A raised FVIII plasma activity is an important feature of the metabolic syndrome and a putative co-factor of HAART induced cardiovascular events. Thus the prevention of the HAART-induced cardio-vascular events should probably not be exclusively focused on atherosclerosis but likewise on the thrombus formation process.
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PMID:Correlations between carotid IMT, factor VIII activity level and metabolic disturbances: a cardio-vascular risk factor in the HIV positive persons. 1750 79

The authors made a qualitative cytological analysis of the percentage of the heterogenic endothelium and its association with the severity of atherosclerosis. A total of 15,000 endotheliocytes (usual-type, giant uninucleated, binucleated, trinucleated, multinucleated, and horseshoe-shaped nuclei) were studied above different forms of atherosclerotic lesion of the human aorta and pulmonary artery. The material was obtained from 5 deceased patients aged 35 to 85 years. Both uninucleated and multinucleated cells were identified as the endothelium by an immunohistochemical test in the detection of specific factor VIII antigen in their cytoplasm. The proportion of heterogenic cells above the intact portions of the pulmonary artery and aorta was ascertained to be 13.7 and 24.8%, respectively; at the same time that of this endothelium above the fatty streaks increased up to 56.1 and 58.7%, respectively; and that above fatty plaques did up to 72.2 and 73.1%, respectively. Thus, the total number of endotheliocytes with the usual type of nuclei statistically significantly decreased above atherosclerotic lesions (fatty streaks and plaques) of the pulmonary artery and aorta to 35.8 and 31.8%, respectively. Extrusion of a population of cells with the usual type of nuclei with the progress of atherosclerotic lesions is attended by an increase in the proportion of the heterogenic endothelium up to 64.2 and 68.2%, respectively. It is suggested that the optimum combination of variable dimensions of the endothelium and the size and number of their nuclei is an adaptive reaction and an essential prerequisite to the most effective endothelial function when atherosclerotic lesion of the arterial intima progresses.
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PMID:[Analysis of the heterogenicity of cytological and morphometric indices of the endothelial nuclei of the aorta and pulmonary artery in atherosclerosis]. 1872 32

To examine the associations of three understudied hemostatic factors--D-dimer, factor VIII(c), and plasmin-antiplasmin (PAP) complex--with incident cardiovascular disease (CVD) and all cause mortality in the Multiethnic Study of Atherosclerosis cohort. Hemostatic factors were measured at baseline in 45-84-year-old patients (n = 6,391) who were free of clinically recognized CVD. Over 4.6 years of follow-up, we identified 307 CVD events, 207 hard coronary heart disease events, and 210 deaths. D-dimer, factor VIII(c), and PAP were not associated with CVD incidence after adjustment for other risk factors. In contrast, each factor was associated positively with total mortality, and D-dimer and factor VIII(c) were associated positively with cancer mortality. When modeled as ordinal variables and adjusted for risk factors, total mortality was greater by 33% (95% CI 15-54) for each quartile increment of D-dimer, 26% (11-44) for factor VIIIc, and 20% (4-38) for PAP. This prospective cohort study did not find D-dimer, factor VIII(c), or PAP to be risk factors for CVD. Instead, elevated levels of these three hemostatic factors were associated independently with increased risk of death. Elevated D-dimer and factor VIII(c) were associated with increased cancer death.
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PMID:Associations of factor VIIIc, D-dimer, and plasmin-antiplasmin with incident cardiovascular disease and all-cause mortality. 1947 1

Valproic acid is one of the most frequently prescribed antiepileptic drugs for the therapy of generalized and focal epilepsies. Valproate induces a variety of hemostatic disorders such as thrombocytopenia, abnormal platelet function, hypofibrinogenemia, and decreased concentrations of von Willebrand factor, and it rarely causes serious bleeding complications. It may also lead to atherosclerosis and thrombosis. However, there is still lack of knowledge about the incidence and occurrence of these particular side effects. In this prospective systematic study, we assessed the early effects of sodium valproate on both pro- and anticoagulatory factors, homocysteine, and lipoprotein (a) in 24 newly diagnosed epileptic children treated with valproate. Valproate causes decreased factor VII levels, platelet count, factor VIII, Protein C, fibrinogen, and increased lipoprotein (a) levels. To the best of our knowledge, our report is the first in the medical literature, which describes that valproate significantly reduces factor VII levels even during short-term therapy.
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PMID:Valproate-associated coagulopathies in children during short-term treatment. 1948 38

The development of peripheral artery disease (PAD), a marker for systemic atherosclerosis and ischemic risk, is an increasingly important concern in the aging hemophilia population. A growing body of data suggests that an absence or deficiency of factor VIII or factor IX may not protect against atherogenesis, implying that the prevalence of PAD in men with hemophilia (MWH) may be higher than previously believed. This article describes special considerations in PAD screening, risk-factor modification, and management in older MWH.
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PMID:An algorithmic approach to peripheral artery disease in hemophilia: extrapolation of management principles from noncoagulopathic patients. 2214 51

Thromboembolism is a complication of hematopoietic stem cell transplant. However, a literature search showed no previous reports of cerebral infarction during the thrombocytopenic stage after hematopoietic stem cell transplant. A 35-year-old woman with acute lymphoblastic leukemia (precursor B-cell type) was treated with hematopoietic stem cell transplant after induction and consolidation chemotherapy. On day 2 after transplant, she was unconscious, and had urinary incontinence and left hemiplegia. A computed tomography scan of the brain showed an acute ischemic infarct in the right middle cerebral artery region and an old infarct at the left thalamus without atherosclerosis. Factor VIII level was elevated (190%; normal range, 60% to 150%). She was treated with rehabilitation and low-dose aspirin. At 6 months after transplant, the leukemia remained in remission and she had no further thromboembolic events. This case suggests that prudent treatment of patients who have hematopoietic stem cell transplant may include monitoring for thromboembolism and testing factor VIII level before transplant.
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PMID:Acute cerebral infarct with elevated factor VIII level during the thrombocytopenic stage after hematopoietic stem cell transplant. 2470 51


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