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

Oxidation of lipoproteins, and, in particular, low-density lipoproteins (LDL), has been shown to play a significant role in the pathogenesis of atherosclerosis. Oxidized LDL are endocytosed via scavenger receptors to form lipid-laden foam cells. The non-enzymatic reaction of glucose with proteins and lipoproteins results in a modified LDL involved in the pathogenesis of late complications in diabetes mellitus. In the present paper, the influence of various E-series prostaglandins (PGE1; 13,14-dihydro PGE1; 13,14-dihydro 15-keto PGE1; and PGE2) on oxidation of native and glycated LDL was investigated. The effect of these agents in the concentration range from 1 pg/mL to 1.6 micrograms/mL on copper-induced oxidation of native and glycated LDL was tested. The concentration of each agent causing the maximal effect on oxidation of native LDL, as measured by the formation of thiobarbituric acid-reacting substances, was chosen to estimate the effect on 2, 4, 8, and 24 h oxidation of glycated LDL. The study was performed with LDL isolated by sequential ultracentrifugation from normolipidemic individuals. LDL (0.25 mg protein/mL) was oxidatively modified with 5 microM CuSO4. The glycosylation of LDL was performed by incubation of LDL with 500 mM glucose for varying periods of time ranging from 10 to 31 days. Our results show that only 13,14-dihydro PGE1 significantly inhibits copper-induced oxidation of native LDL, while the other examined E-series prostaglandins in vitro are ineffective as reducing agents in LDL-oxidation.
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PMID:Do E-series prostaglandins and their metabolites influence oxidation of native and glycated low-density lipoproteins? 966 Dec 19

We have established a novel photochemical model of intimal thickening in the rat femoral artery. The endothelium was injured by the photochemical reaction between rose bengal and green light, which was followed by thrombotic occlusion, vascular smooth muscle cells (VSMC) migration and proliferation. The neointima was formed by proliferated VSMC and the extracellular matrix, reaching to maximal thickness within 3 weeks after the endothelial injury. Using this model, we have investigated the effect of several anti-proliferative drugs, anti-allergic drugs, angiotensin converting enzyme inhibitors, prostaglandin E1, anti-thrombotics, or leukotrienes receptor antagonists, on intimal thickening. This model has two major advantages in comparison with other methods: one is that the media is free from mechanical stress, and the model is expected to represent pathological changes close to clinical atherosclerosis. Another advantage is that this method is also applicable to small animals such as mice, including transgenic mice. These advantages are very helpful for investigating the mechanism of atherogenesis.
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PMID:[A novel photochemical model of intimal thickening in the rat femoral artery and evaluation of anti-proliferative drugs]. 966 84

Extracellular matrix remodelling occurs during atherosclerosis dictating the structure of the plaque and thus the resistance to rupture. Monocytes and macrophages are believed to play a role in this remodelling. In the present study, filter-separated co-culture has been used to study the effect of monocytes on procollagen turnover by human vascular smooth muscle cells (VSMC). In this system, freshly isolated human peripheral blood monocytes inhibited procollagen secretion from VSMC without affecting either degradation of procollagen, or DNA synthesis by the VSMC. Insertion of a 12 kDa dialysis membrane between the two cell types and treatment with indomethacin showed that the inhibitory factor was of low molecular weight and was cyclooxygenase-dependent. Pre-incubation of each cell type with indomethacin demonstrated that monocyte, but not VSMC cyclooxygenase was required. Thus, the inhibitory effect on procollagen secretion was due, most likely, to monocyte prostaglandins. Neither inhibition of thromboxane synthetase, nor blocking IL-1 activity, reduced the inhibitory activity. Addition of prostaglandins PGE1, PGE2 and PGF2alpha to VSMC cultures caused a reduction in procollagen secretion which was equivalent to, but was not additive with, the maximal effect achieved by monocytes. Monocytes and macrophages are a major source of prostaglandins and these molecules are likely to play an important role in collagen turnover within lesions.
Atherosclerosis 1999 Feb
PMID:Monocyte prostaglandins inhibit procollagen secretion by human vascular smooth muscle cells: implications for plaque stability. 1003 Mar 79

Monocyte/macrophages produce a variety of substances which may influence the function of smooth muscle cells (SMC). During atherogenesis, macrophages are thought to modulate SMC migration, proliferation and synthesis of extracellular matrix. Such modulation is the balance between stimulatory and inhibitory influences. Thus, for example, our earlier studies have shown that macrophages not only secrete mitogens, but also produce small molecular weight inhibitors of SMC proliferation. In the present study, we have used a co-culture system in which human monocyte/macrophages were separated from human arterial SMC (hSMC) by a filter with the optional addition of a 12 kDa cut-off dialysis membrane, in order to assess their effect on hSMC growth. We have found that human peripheral blood-derived monocytes produced a substance of < 12 kDa that inhibited hSMC growth in the co-culture system. The monocyte-derived factor causing this effect was completely blocked by indomethacin, indicating that growth-inhibitory factors produced by the monocytes were cyclooxygenase products. We have shown that PGE1 and PGE2 inhibit hSMC growth, making them likely candidates for the effector molecules released from monocytes in our co-culture system.
Atherosclerosis 1999 Jul
PMID:Inhibition of human arterial smooth muscle cell growth by human monocyte/macrophages: a co-culture study. 1042 6

Previous studies have shown that oral administration of 300 mg alpha-tocopherol/day to healthy volunteers decreases platelet function and enhances their sensitivity to the platelet inhibitor, prostaglandin E(1), when full dose-response curves to a range of agonist concentrations are made. In this study, the effects of oral doses of natural alpha-tocopherol (75, 200 and 400 IU/day) were studied in order to determine whether the same effects might be achieved with lower intakes of vitamin E and whether inhibition is related to the platelet levels of the antioxidant in platelet membranes. Twenty two subjects undertook the supplementation regime, divided into three units of 2 weeks, each cycling through each of the dosages. The results show that uptake of vitamin E by the platelets was optimal at 75 IU/day, correlating with the maximal influence on platelet aggregation and platelet responsiveness to inhibition by PGE1, increased supplemental levels exerting no greater effects.
Atherosclerosis 1999 Nov 01
PMID:Moderate supplementation with natural alpha-tocopherol decreases platelet aggregation and low-density lipoprotein oxidation. 1052 39

The in vitro and in vivo effects of prostaglandin E1 on cholesterol ester hydrolase (CEase) and lipase [glycerol ester hydrolase (GEH)] activity in human serum were examined. Cholesterol esterase and lipase activity in the sera of men with atherosclerosis differed substantially from that in the control subjects. CEase activity was raised and GEH activity suppressed in the serum of men with atherosclerosis compared with controls. Prostaglandin E1 in vitro was found to suppress lipase but to increase cholesterol esterase activity to some extent. However, in vivo activities of GEH and CEase in the sera of men with chronic arterial occlusions of the lower limbs treated with prostaglandin E1 revealed that lipase activity was increased but that cholesterol esterase activity was unchanged. Recent studies have demonstrated that by altering the metabolic pathways of acylcholesterols and triacylglycerols, prostaglandin E1 may lead to the development of new strategies for retarding atherosclerosis.
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PMID:Prostaglandin E1 influences serum cholesterol esterase and lipase activity in different ways. 1064 15

Data from our in vitro studies indicate that macrophages isolated from mice fed GLA-enriched diets inhibit vascular SMC proliferation via a PGE1-cAMP dependent mechanism. Since SMC proliferation is one of the main events implicated in the pathogenesis of atherosclerosis (Ross, 1993), this anti-proliferative effect observed by dietary GLA is noteworthy. In vivo studies have established that dietary GLA is capable of retarding the atherosclerotic lesion formation in ApoE knock out mice, an animal model that develops atherosclerosis similar to humans (Reddick, 1994). We propose that dietary GLA has the potential to inhibit SMC proliferation leading to retardation of atherosclerotic lesion formation, and therefore favorable modulation of the atherogenic process.
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PMID:Modulation of atherogenesis by dietary gamma-linolenic acid. 1066 72

In vascular pathology, the discovery of the ABC1 receptor (ATP-binding-cassette transporter 1), the deficit of which is responsible for Tangier disease and familial hypoalphalipoproteinaemias, has opened the greatest perspectives with the possibility of new active treatments in the prevention of atherosclerosis. Other advances were more expected. A large British trial convincingly demonstrated that the follow-up of small abdominal aortic aneurysms is reliable. The MEDENOX trial showed the value of prophylaxis of thromboembolic disease in a medical setting and the reduced incidence of phlebographic events. The ICAI study, on the other hand, showed the difficulty of treatment of critical ischaemia of the lower limbs: alprostadil (PGE1) was ineffective with a 6 month follow-up in this pathology. Finally, low dose aspirin is at least as effective as high doses.
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PMID:[The best of vascular pathology in 1999]. 1072 52

Infusional, cyclic PGE1 treatment is effective in patients with intermittent claudication and critical limb ischemia (CLI). One of the problems related to chronic PGE1 treatment in vascular diseases due to atherosclerosis is to evaluate the variations of clinical conditions due to treatment in order to establish the number of cycles per year or per period (in severe vascular disease reevaluation of patients should be more frequent) needed to achieve clinical improvement. In a preliminary pilot study a group of 150 patients (mean age 67+/-12 years) with intermittent claudication (walking range from 0 to 500 m) and a group of 100 patients with CLI (45% with rest pain, and 55% gangrene; mean age 68 +/-11 years) the number of PGE1 cycles according to the short-term protocol (STP) needed to produce significant clinical improvement was preliminarily evaluated. Considering these preliminary observations, the investigators established a research plan useful to produce nomograms indicating the number of cycles of PGE1-STP per year needed to improve the clinical condition (both in intermittent claudication and CLI). A significant clinical improvement was arbitrarily defined as the increase of at least 35% in walking distance (on treadmill) and/or the disappearance of signs and symptoms of critical ischemia in 6 months of treatment in at least 75% of the treated patients. With consideration of the results obtained with the preliminary nomograms a larger validation of the nomograms is now advisable. A cost-effectiveness analysis is also useful to define the efficacy of treatment on the basis of its costs. The publication of this report in two angiological journals (Angeiologie and Angiology) will open the research on nomograms to all centers willing to collaborate to the study. The data are being collected in the ORACL.E database and will be analyzed within 12 months after the publication of this report.
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PMID:Nomograms used to define the short-term treatment with PGE(1) in patients with intermittent claudication and critical ischemia. The ORACL.E (Occlusion Revascularization in the Atherosclerotic Critical Limb) Study Group. The European Study. 1095 6

There is evidence that the coagulation system is activated in patients with peripheral arterial occlusive disease (PAOD). The beneficial effects of the vasoactive drug prostaglandin E1 (PGE1) may rely in part on the modulation of the coagulation system. The study was designed to evaluate the effects of PGE1 on hemostatic and fibrinolytic variables in patients with intermittent claudication. Therefore molecular markers of thrombin (prothrombin fragment 1+2, PTF 1+2; thrombin-antithrombin III complexes, TAT) and fibrin formation (fibrinopeptide A, FPA) and markers of the fibrinolytic activity (fibrin degradation products, D-dimers) were determined before and immediately after the first PGE1 dose (60 microg in 100 ml NaCl over 2 h i.v.) as well as after 4 weeks of daily infusion therapy in 12 PAOD patients and in eight control patients before and after a single placebo infusion. Plasma levels of PTF1+2, TAT, FPA and D-dimers tended to decrease after the initial dose of PGE1. Infusion therapy with PGE1 for 4 weeks led to a decrease of all hemostatic and fibrinolytic parameters with most pronounced changes for PFT1+2, D-dimers and plasminogen activator inhibitor-1 decreasing by 11% (P<0.05), 20% (P<0.05), and 7% (P<0.05), respectively. These variables remained unchanged in controls with placebo infusion. In summary, infusion therapy with PGE1 in patients with PAOD reduces thrombin formation and results in a decrease of fibrin degradation. PGE1 may thus reduce fibrin deposition involved in the pathogenesis of atherosclerosis.
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PMID:Hemostasis and fibrinolysis in patients with intermittent claudication: effects of prostaglandin E1. 1109 Feb 53


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