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

The hydroxylated derivatives of polyunsaturated fatty acids may be potent modulators of basic biological responses involved in pathological processes, including atherosclerosis. The object of the present investigation was to study the effects of monohydroxylated fatty acids (namely 12-HETE) on the properties of aortic smooth muscle cells (SMC) in culture. The changes in cell expression of differentiation antigen alpha-SM actin and 2P1A2 was followed by computerized morphometry, using specific monoclonal antibodies and the activation of cells by measuring cell motility. In addition, intracellular [Ca2+]i mobilization and IP3 formation were studied. Finally, the metabolic routes of monohydroxylated compounds and their effects on PGI2 secretion were reported. The results demonstrate that 12-HETE is able to stimulate the phenotypic modulation. PGI2 production and motility of arterial SMCs, despite any detectable activity in increasing [Ca2+]i or IP3 formation. By contrast with parent compounds 15-HETE and 13-HODE, which appear as potent prodifferentiating molecules, 12-HETE is specifically metabolized via a 10-11 reductase pathway in addition to the classical beta-oxidation pathway. Taken together, our results suggest that cellular metabolism of 12-HETE, produced by platelets in the vicinity of the arterial intima, and also by cells present inside the atherosclerotic intima, or associated with modified LDL may play a key role in the atherosclerotic process.
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PMID:Effects of monohydroxylated fatty acids on arterial smooth muscle cell properties. 163 75

The effects of the orally active prostacyclin mimetic cicaprost on morphologic and functional alterations of rabbit aorta was investigated in experimental hypercholesterolemia. Oral cicaprost resulted in a significantly reduced aortic atheromatous plaque formation and partially prevented hypercholesterolemia-induced impairment of endothelium-dependent relaxations. It is concluded that long-term substitution with PGI2 may beneficially influence the progression of atherosclerosis.
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PMID:Antiatherosclerotic properties of oral cicaprost in hypercholesterolemic rabbits. 163 2

Oral treatment of cholesterol-fed rabbits with the PGI2 mimetic cicaprost largely reduces hypercholesterolemia-induced platelet and neutrophil hyperreactivity. In addition, cicaprost prevents atherosclerosis-induced platelet desensitization for PGI2. These effects persist after cicaprost treatment is withdrawn. Since platelets and leukocytes are supposed to contribute to atherogenesis, this suggests a favourable effect of long-term oral PGI2 substitution in hypercholesterolemia.
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PMID:Oral cicaprost reduces platelet and neutrophil activation in experimental hypercholesterolemia. 163 3

Reduced prostacyclin (PGI2) production by the vascular wall may play an important role in the pathogenesis of vascular lesions such as atherosclerosis. The present study was undertaken to evaluate the effect of vitamin E on the production of PGI2 and other prostaglandins (prostaglandin E2 [PGE2], thromboxane A2 [TXA2], and 15-hydroxyeicosatetraenoic acid [15-HETE]) by bovine aortic endothelial cells cultured in a high concentration of glucose (300 mg/dL). Compared with endothelial cells cultured in 100 mg/dL glucose, the production of PGI2 and other prostaglandins, except 15-HETE, was significantly reduced in cultures containing 300 mg/dL glucose when stimulated by histamine, the Ca2+ ionophore, A23187, or human plasma-derived serum (PDS). The addition of vitamin E to each stimulant significantly restored the production of PGI2, PGE2, and TXA2, products of the cyclo-oxygenase pathway, in aortic endothelial cells cultured in 300 mg/dL glucose. This effect of vitamin E on the stimulation of prostaglandin production was generally specific for D-alpha-tocopherol, but not for the other vitamin E analogs tested. However, vitamin E and the stimulants had no effect on the production of 15-HETE, a product of the lipoxygenase pathway. Moreover, vitamin E alone, without stimulants, did not affect prostaglandin production in cultured bovine aortic endothelial cells. These results suggest that vitamin E may restore reduced PGI2, PGE2, or TXA2 production by bovine aortic endothelial cells cultured in a high concentration of glucose. It seems likely that vitamin E may restore depressed PGI2 production by the vascular wall in hyperglycemic conditions such as those seen in patients with diabetes mellitus.
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PMID:Vitamin E restores reduced prostacyclin synthesis in aortic endothelial cells cultured with a high concentration of glucose. 164 Aug 48

Tissue factor (TF) which initiates clotting process can be expressed by stimulated endothelial cells (EC). TF is an apolipoprotein requiring an association with phospholipids (PL) in order to become active. Also PL constitute an important storage pool of polyunsaturated fatty acids (PUFAs) in EC which can be modulated by diet or cell medium supplementation. In order to test the effect of such manipulation upon TF activity, we have pre-enriched human EC cultures with different fatty acids of nutritional interest. TF was evaluated after 4 h of thrombin stimulation by using a chromogenic method. Without additional stimulating agents, these acids have no effect on the basal level of TF. Eicosapentaenoic and docosapentaenoic acids appeared to be ineffective at the stimulated TF level. Only adrenic acid (22:4(n-6)) has been found to significantly enhance TF activity of thrombin-stimulated endothelial cells. Other TF inducers were also tested after 22:4(n-6) enrichment. An increase tendency of TF expression was found only with tumor necrosis factor, whereas interleukin-1 beta, lipopolysaccharide and especially phorbol myristate acetate stimulations were not significantly modified. The priming effect of adrenic acid on thrombin stimulated TF expression might involve alterations of signal transduction pathways rather than modifications of apolipoprotein III environment. Adrenic acid, which is a prostacyclin inhibitor, appears to be potential prothrombotic agent.
Atherosclerosis 1992 Jul
PMID:Priming effect of adrenic acid (22:4(n-6)) on tissue factor activity expressed by thrombin-stimulated endothelial cells. 164 92

Atherosclerosis can be defined in broad terms as a vascular disease accompanied by dysregulation of cholesterol metabolism and the accumulation of smooth muscle cells and macrophages within the vessel wall. At the interface of the blood and the vessel wall is the endothelium, which actively participates in a plethora of critical homeostatic functions in addition to affecting cholesterol trafficking in the underlying smooth muscle cell and macrophage. These events include: 1) inflammation resulting in release of cytokines, 2) changes in vascular reactivity causing release of endothelial cell derived relaxing factor (EDRF) and PGI2, and 3) control of vascular smooth cell proliferation via release of growth factors and growth suppressor molecules. Each process has been linked to the regulation of cholesterol accretion in the arterial cell. Furthermore, each homeostatic process is regulated by transmembrane signaling mechanisms at the lipid-protein interface of the membrane. Data have emerged recently indicating that biological response modifiers that trigger transmembrane signaling work in a sequential manner to control cell function. We review studies of the regulatory mechanisms of transmembrane signal transduction that advance the concept that phosphorylation of the specific protein components of the receptor machinery may result in a cooperative cellular response to ligands that will ultimately affect cholesterol delivery and trafficking within cells. We review recent data demonstrating that eicosanoids and cytokines released from one cell activate their receptors on neighboring cells, and interact with each other during this "cross-talk phenomenon." Cross-talking among phosphorylation reactions involving, for example, protein kinases A and C and tyrosine protein kinase, coupled with the highly regulated eicosanoid pathways and the diacylglycerol-phosphatidyl inositol (DG-PI) system, are discussed in terms of their metabolic impact on cholesterol delivery, intracellular processing, and efflux.
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PMID:Signal transduction in atherosclerosis: integration of cytokines and the eicosanoid network. 164 57

The purpose of this study was to determine whether the generation of a neointima, an early step in the development of atherosclerosis, affects endothelium-dependent or -independent vasodilation. The neointima was induced, within 7 days, by positioning a nonocclusive silicone collar around one carotid artery in rabbits. After 1, 2, 7, or 14 days segments were cut from the collar-surrounded region of this artery as well as from the sham-operated contralateral artery and were used for isometric tension recording or for bioassay of nitric oxide (NO). The acetylcholine-induced release of NO was significantly reduced at 7 days. The tension recordings suggested that this already occurred at the earliest stages of neointima formation. Neither the capacity of the endothelial cells to form NO in response to the calcium ionophore A23187 nor the capacity of the underlying smooth muscle cells to relax in response to sources of exogenous NO (3-morpholinosydnonimine and nitroglycerin) was affected by the neointima. Therefore, the impaired endothelium-dependent relaxations to acetylcholine are presumably due to a defect at the level of the endothelial muscarinic receptors. The presence of a fully developed neointima did not alter the responsiveness to isoproterenol and forskolin but enhanced prostacyclin-mediated responses (assessed by iloprost and 13-hydroxyoctadecadienoic acid). These results illustrate selective alterations of endothelial and smooth muscle cell function in intima generation before fatty streak formation.
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PMID:Neointima formation impairs endothelial muscarinic receptors while enhancing prostacyclin-mediated responses in the rabbit carotid artery. 164 34

It has been generally accepted that platelets play etiological roles for the development of atherosclerosis and arterial thrombosis. Platelet activation may be dependent upon the cytosolic free Ca2+ concentration ([Ca2+]i), and regulated by PGI2 and endothelium-derived relaxing factor (EDRF) released by vascular endothelium. We have studied here the effect of endothelial cells (EC) on platelet activation and intracellular Ca2+ mobilization. Effluent of non-stimulated EC column inhibited thrombin-induced platelet aggregation and intracellular Ca2+ mobilization. An addition of this effluent to platelet suspension leaded to increase in intraplatelet cyclic AMP (cAMP) which was inhibited by the treatment of indomethacin to EC, suggesting that this effect was involved in PGI2 released by EC. On the other hand, effluent of thimerosal-stimulated EC column inhibited platelet aggregation and increase in [Ca2+]i stimulated with thrombin, and leaded to increase in intraplatelet cyclic GMP (cGMP). But the treatment of indomethacin to EC had no effect of this inhibition. The effect of thimerosal-stimulated EC was inhibited by the addition of 1-NG-monomethylarginine (NMA), EDRF/NO inhibitor, suggesting that EDRF released by thimerosal-stimulated EC produced an increase in cGMP and inhibited platelet activation. Although forskolin-induced in cAMP caused a marked prevention of inositol 1, 4, 5-trisphosphate (IP3) production stimulated with thrombin, 8-bromo cGMP and EDRF-induced increase in cGMP had no effect of IP3 production. An increase in cAMP and cGMP was considered to inhibit intracellular Ca2+ mobilization by different mechanisms in platelets.
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PMID:[Intracellular Ca2+ mobilization and its regulation in platelet activation]. 165 28

Human aortic endothelial cells, isolated at autopsy from a 52-year-old male dying from lung cancer, were treated with simian virus 40 (SV40). One colony was isolated from the infected endothelial cell culture 4 weeks after infection. The cells expressed SV40 large T antigen and p53 protein (p53) in their nuclei but lacted the characteristics of a transformed phenotype. The cells grew well in a monolayer over the 97th passage and exhibited Factor VIII-related antigen, Ulex europaeus 1 agglutinin (UEA-1) as endothelial cell markers, and a well-developed fibronectin network. The amount of prostacyclin synthesized by the cells was less than the amount synthesized by normal aortic or umbilical cord vein endothelial cells. The cells produced relatively large amounts of procollagenase, and 12-o-tetradecanoyl-phorbol-13-acetate (TPA) augmented the ability of the cells to produce this enzyme. These immortalized human aortic endothelial cells, which have some characteristics of normal endothelial cells and, like capillary endothelial cells, have the ability to produce collagenase, will probably prove useful for studies of atherosclerosis and angiogenesis.
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PMID:Collagenase production by immortalized human aortic endothelial cells infected with simian virus 40. 167 13

To investigate the functional alteration of human aortic endothelial cells with aging, prostacyclin synthesis was qualitatively and quantitatively examined. The endothelial cells of human aortas and umbilical veins or inferior vena cavae were immunohistochemically examined and found positive for prostacyclin, but the intensity of aortic endothelial cells from older subjects was low. In addition to the endothelial cells, smooth muscle cells in the thickened intima, not the media, of the aorta were also immunoreactive. Endothelial cells were successfully cultured from human aortas obtained from infants through aged subjects and were subdivided into three groups: young, middle, and old. Prostacyclin synthesis by endothelial cells from all types of blood vessels was extremely great at the primary culture, but decreased abruptly in the following subcultures. Among the aortic endothelial cells, the young group synthesized the largest amount of prostacyclin in a conventional culture condition, with synthesis progressively decreasing in the older groups. The in vitro prostacyclin biosynthesis was supported by the qualitative analysis on the tissue sections. These results indicate that prostacyclin synthesis of the aortic endothelial cells decreases with age, but intimal smooth muscle cells potentially have a back-up mechanism and substitute this synthesis to some extent. The decreased synthesis of prostacyclin with age may play an important role in the development and advancement of thrombosis and atherosclerosis.
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PMID:Age-related decline in prostacyclin synthesis by human aortic endothelial cells. Qualitative and quantitative analysis. 170 40


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