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

Vascular endothelial cells (ECs) are not merely a selective permeability barrier between blood and underlying tissue but actively play an important role in maintaining homeostasis of circulation. ECs that have a variety of synthetic, metabolic, secretory and self-adaptive capabilities regulate vascular tonus and interact with other cells such as vascular smooth muscle cells and white cells. Recent evidence suggests that these functions are affected by shear stress on the endothelial wall, which is a rheological force shearing the luminal surface of the blood vessel when a viscous fluid such as blood flows over it. Wall shear stress reportedly regulates adaptive vessel growth and angiogenesis, and might be a local risk factor in the pathogenesis of atherosclerosis. Shear stress also modulates the production of vasoactive substances such as endothelium-derived relaxing factor, prostacyclin, histamine and endothelin, and regulates macromolecule permeability and endocytosis. More recent studies have shown that shear stress exerts an influence on the expression of mRNA such as tissue plasminogen activator mRNA. These facts suggest that ECs serve as mechanoreceptors by which changes in blood flow or shear stress are recognized by the EC and the signal is transmitted to intracellular organelles. It has been indicated so far that intracellular Ca2+ and the membrane potential might be involved in the shear stress-sensing mechanism of ECs. Knowledge of EC biomechanics, i.e. the EC response to shear stress, will help us to understand the mechanism not only of blood flow-dependent vessel growth and remodeling but also atherogenesis.
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PMID:Blood flow and vascular endothelial cell function. 813 12

This study of 49 patients with spontaneous venous and arterial thrombosis identified 27 with hypercoagulable states: 13 had only venous thrombosis (VT), six had episodes of VT followed by arterial thrombosis (AT) and eight had AT only. All 27 patients were less than 42 years of age; 22 had specific natural anticoagulant or fibrinolytic deficiencies: antithrombin III (nine patients), protein C (eight patients), protein S (three patients), heparin cofactor II (two patients), tissue plasminogen activator release (one patient) and mixed antithrombin III and protein S (one patient). The remaining five patients had recurrent thrombotic events associated with resistance to heparin anticoagulation, but no established laboratory diagnosis. Clotting complications included recurrent VT, pulmonary embolism, multiple failed arterial procedures and lower extremity amputation. The remaining 22 patients (mean age of 53 years, range of 46 to 63 years), 12 with VT and ten with AT, did not have laboratory evidence of hypercoagulability and none had recurrent vascular occlusions. All these patients were successfully treated by conventional therapy without any additional thrombotic events during the follow-up period. Young adults with spontaneous thrombotic events should be screened for possible hypercoagulable states. Additionally, these young patients need further evaluation and treatment of cardiovascular risk factors. Those with premature atherosclerosis have an especially poor prognosis despite surgical intervention and anticoagulant therapy.
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PMID:Hypercoagulable states as an evolving risk for spontaneous venous and arterial thrombosis. 792 7

Recent advances in determining anti-thrombogenic functions of vascular endothelial cells are reviewed. The following anticoagulant and fibrinolytic systems of endothelial cells are physiologically important; (1) Endothelial cell-derived metabolites including prostacyclin and nitric oxide (NO) support platelet inactivity. (2) Antithrombin III and tissue factor pathway inhibitor (TFPI) bound to heparin-like proteoglycans on endothelial cell membrane inhibit activated serine protease coagulation factors such as thrombin, factor Xa and factor VIIa-tissue factor complex. (3) Thrombomodulin converts thrombin from procoagulant into anticoagulant. Thrombin associated to thrombomodulin on endothelial cells activates protein C. Activated protein C in concert with protein S bound to endothelial cell membrane inactivates factors Va and VIIIa. (4) A receptor for both tissue plasminogen activator and plasminogen on endothelial cells provides an efficient plasmin generating system. Perturbation of these anti-thrombogenic systems of endothelial cells is caused by endotoxin (LPS), cytokines such as interleukin-1 and tumor necrosis factor (TNF), and risk factors for atherogenesis including lipoprotein(a) and homocysteine may result in arterial or venous thrombosis with subsequent development of atherosclerosis.
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PMID:[Anticoagulant and fibrinolytic systems of the injured vascular endothelial cells]. 817 40

The low-density lipoprotein receptor-related protein (LRP) is a multifunctional receptor that binds to apolipoprotein E-rich lipoproteins, lipoprotein lipase, alpha 2-macroglobulin, lactoferrin, and tissue plasminogen activator. We studied the mRNA expression of LRP in human monocyte-derived macrophages and THP-1 cells. mRNA expression of LRP was induced during cell differentiation from human monocytes to macrophages or after incubation with phorbol ester (tetradecanoylphorbol acetate 100 ng/mL) in THP-1 cells, and the addition of 30 ng/mL macrophage colony-stimulating factor further enhanced LRP expression. These results indicated that the expression of LRP depended on the stage of differentiation and maturation of monocytic cells. mRNA expression of LRP was also enhanced in human monocyte-derived macrophages in the presence of acetylated low-density lipoprotein and in aorta of rabbits fed a high-cholesterol diet. We hypothesize that the LRP induced in monocyte-derived macrophages is involved in the initial process of atherosclerosis by interacting with its multiple ligands.
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PMID:Induction of LDL receptor-related protein during the differentiation of monocyte-macrophages. Possible involvement in the atherosclerotic process. 819 72

The effect of different fat loads on postprandial lipemia and hemostatic activity was examined in 10 middle-aged men using 3 different meals. One meal was rich in saturated fatty acids (cream), the other rich in n-6 polyunsaturated fatty acids (sunflower oil) and the third was fat-free containing only carbohydrates. Lipoprotein lipids and hemostatic parameters were measured during fasting and 2, 4, 6 and 8 h after the test meal. In fasting samples, several hemostatic parameters were significantly associated with lipoprotein lipids. Most notable were the strong associations of fibrinolysis parameters tissue plasminogen activator antigen and plasminogen activator inhibitor activity (PAI-1) with total and very low density lipoprotein (VLDL) triglycerides. During lipemia, the associations were approximately similar or slightly weaker than in the fasting state. Both fat loads resulted in similar postprandial lipid responses: VLDL and high density lipoprotein (HDL) triglycerides reached maximum at 4 h after the meal. VLDL cholesterol also increased 4 and 6 h after the fat loads. HDL3 cholesterol declined after the fatty meals but no change was observed in the HDL2 fraction. The fat-free meal gave no significant lipid changes during the time course studied. Factor VII activity (F VII:C) increased 6 and 8 h after the fatty meals, whereas a decrease was observed after the fat-free meal. The changes (+/- S.D.) at 8 h after cream, sunflower oil and fat-free meal were 5.2 +/- 3.3, 3.3 +/- 4.2 and -5.8 +/- 7.9 percentage points, respectively, and the effect of the meal on the changes was statistically significant (F (8,99) = 2.99, P = 0.0048). F VII antigen (F VII:Ag) tended to decline during the day but there was no difference between the meals. Factor VIII activity (F VIII:C) was highest after the polyunsaturated fat meal and lowest after the fat-free meal. PAI-1 declined during the day and the decline tended to be steepest after the fat-free morning meal. The effect of the meal on the changes in lipoprotein lipids and hemostatic factors varied significantly between individuals. In conclusion, postprandial lipemia after a single fatty meal was associated with procoagulatory change in F VII:C but there was no difference between saturated fat and n-6 polyunsaturated fat.
Atherosclerosis 1993 Oct
PMID:The effects of saturated fat and n-6 polyunsaturated fat on postprandial lipemia and hemostatic activity. 828 Jan 80

In order to investigate processes, such as atherosclerosis and inflammation in vitro, it is necessary to obtain viable and pure endothelial cell cultures from human hearts. To this end, endothelial cells were isolated and cultured from the micro- and macrovasculature of human hearts obtained during heart transplantation. Isolation of capillaries after enzymatic digestion of heart muscle provided a source of microvascular endothelial cells. Contaminating non-endothelial cells were removed by a new technique: paramagnetic beads linked to the lectin ulex europaeus I (UEA-I) were used to select endothelial cells. The resulting cultures contained less than 2% of non-endothelial cells, as judged from immunological staining and fluorescence-activated cell sorting. Both types of endothelial cell displayed typical endothelial properties. They were all positive for factor VIII-related antigen and expressed the endothelial-specific adhesion molecules, CD31 and E-selectin (ELAM-1), after stimulation with cytokines. In addition, they could be labelled with Dil-Ac-LDL, contained angiotensin converting enzyme activity and secreted tissue plasminogen activator, thus demonstrating that typical endothelial functions were preserved in culture.
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PMID:Cultivation and characterization of micro- and macrovascular endothelial cells from the human heart. 829 83

Normal blood fluidity and perpetuation of the non-thrombogenic state are primarily maintained by the anticoagulant and fibrinolytic systems of vascular endothelial cells involving heparin-like molecule, thrombomodulin, prostacyclin, and the receptor for tissue plasminogen activator. Atherosclerosis perturbes these activities, resulting in arterial thrombosis. On the other hand, recent experimental evidence suggests that the disordered thromboregulation often promotes atherosclerosis. Several known risk factors for development of atherosclerosis, including homocysteine and lipoprotein (a) perturb anticoagulant and fibrinolytic systems of vascular endothelial cells at an early stage of atherogenesis.
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PMID:[Coagulation and fibrinolytic systems and atherogenesis]. 841 63

Ninety cardiac allograft recipients were studied for clinical and functional parameters during a 40-month period. Baseline histologic and immunocytochemical data were obtained from donors' hearts before transplantation, and serial endomyocardial biopsy specimens were studied histologically for cellular infiltrates and immunocytochemically for complement and immunoglobulin deposits and for components of the hemostatic, fibrinolytic, and natural anticoagulant pathways. Results were grouped according to the time from transplantation: the first 3 months, 4 to 21 months, and 22 to 40 months. Each group was evaluated for most frequently obtained immunocytochemical findings and results relevant to clinical-laboratory cooperation in patient management. During the first 3 months, findings of biopsy specimens from allografts that subsequently were going to be problem cases revealed depleted tissue plasminogen activator in arteriolar smooth muscle cells, and recipient IgM that was deposited on donor endothelium of stable grafts was diminished or absent in unstable allografts. In addition, vascular deposits of activated complement components were identified in 50 of 70 allografts. From 4 through 21 months after transplantation, vascular deposits of complement rarely were identified (even in patients who previously had positive biopsy specimens), and the principal vascular lesion was fibrin deposits with impaired anticoagulant pathways and inadequate fibrinolysis, usually without associated cellular infiltrates. From 22 through 40 months after transplantation, the principal vascular lesion was graft-induced atherosclerosis. These immunocytochemically defined qualitative and quantitative changes in unstable or failing allografts form a time-related spectrum of lesions that encompasses the emerging diagnostic entity of vascular rejection.
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PMID:Laboratory-clinical correlates of time-associated lesions in the vascular immunopathology of human cardiac allografts. 847 82

Several haemostatic factors have been shown to have a predictive role in cardiovascular disease, although their relationship with prevalent peripheral arterial disease is not well reported. Using a random sample of 1592 men and women aged 55-74 years from Edinburgh, Scotland, we examined the relationship of von Willebrand factor (vWF), tissue plasminogen activator (t-PA) and fibrin D-dimer antigens and factor VII activity to peripheral arterial disease. t-PA antigen and fibrin D-dimer showed significant linear trends of increased levels with increasing severity of disease in both sexes (p < or = 0.01) and vWF showed a similar pattern in men only (p < or = 0.01). On multivariate analysis, fibrin D-dimer was independently related to the risk of intermittent claudication (p < or = 0.01) and, among men, to the extent of arterial narrowing in the lower limb, as measured by the ankle brachial pressure index, (ABPI) (p < or = 0.001). These results are further evidence of a role for intravascular fibrin deposition in the development of peripheral atherosclerosis.
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PMID:Fibrin D-dimer, haemostatic factors and peripheral arterial disease. 857 5

Growing evidence suggests that moderately elevated levels of homocysteine are associated not only with arterial thrombosis and atherosclerosis but also with venous thrombosis as well. We have reviewed recent studies that indicate that homocysteine inhibits several different anticoagulant mechanisms that are mediated by the vascular endothelium. The protein C enzyme system appears to be one of the most important anticoagulant pathways in the blood. Homocysteine inhibits the expression and activity of endothelial cell surface thrombomodulin, the thrombin cofactor responsible for protein C activation. Homocysteine inhibits the antithrombin III binding activity of endothelial heparan sulfate proteoglycan, thereby suppressing the anticoagulant effect of antithrombin III. Homocysteine also inhibits the ecto-ADPase activity of human umbilical vein endothelial cells (HUVECS). Because ADP is a potent platelet aggregatory agent, this action of homocysteine is prothrombotic. Homocysteine also interferes with the fibrinolytic properties of the endothelial surface because it inhibits the binding of tissue plasminogen activator. Homocysteine stimulates HUVEC tissue factor activity. We have found that lipoprotein(a) [Lp(a)] also stimulates HUVEC tissue factor activity. The combination of Lp(a) plus homocysteine induced more tissue factor activity than either agent alone. These disruptions in several different vessel wall-related anticoagulant functions provide plausable mechanisms for the occurrence of thrombosis in hyperhomocysteinemia.
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PMID:Homocysteine and hemostasis: pathogenic mechanisms predisposing to thrombosis. 864 72


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