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

This study examines the effect of prostaglandin E2 and 6-keto F1 alpha on the cholesteryl ester metabolism of cells grown in tissue culture. When 3T3 mouse fibroblasts were incubated with cationized low density lipoprotein (LDL) and 3H-labelled oleic and 14C-labelled linoleic acids a marked increase in cholesteryl ester content of cells was observed. Oleic acid was the preferred substrate for cholesterol esterification. However, the presence of prostaglandin E2 or 6-keto F1 alpha (up to 10 micrograms/ml) did not affect the cholesteryl ester content or the uptake of labelled fatty acids into cellular lipids. Following preincubation with cationized LDL and labelled fatty acids the cells were reincubated in normal medium with or without prostaglandins. The presence of PGE2 or 6KPGF1 alpha (up to 10 micrograms/ml) did not appreciably change the rate of removal of cholesteryl ester or labelled lipids. This indicates that these prostaglandins even when present in relatively large doses in the incubation medium do not affect lipid metabolism of cells grown in tissue culture.
Atherosclerosis 1982 Mar
PMID:Absence of effect of prostaglandins on cholesteryl ester metabolism of 3T3 mouse fibroblasts grown in tissue culture. 695 77

The aortas of 9 months aged Show Racer and White Carneau pigeons were examined for their PGE2, PGF2 alpha and 6-keto-PGF1 alpha synthesis from labelled arachidonic acid by radiothinlayer chromatography. The prostacyclin formation was estimated by means of Moncada's bioassay. PGE2 and PGF 2 alpha synthesis in the aorta of pigeons is higher than in rats, whereas less 6-keto-PGF1 alpha is formed in pigeon aortas. The susceptible White Carneau pigeons synthesitize more prostaglandins than the resistant Show Racer pigeons. PGI2 and 6-keto-PGF 1 alpha-formation is extremely low in avian arota. These data are in part contradicting to our findings im mammalians (where the atherosclerosis susceptible animals generate less PGI2) and warrants sequential measurements of prostaglandin synthesis in aorta to assess its significance during various stages of atherogenesis.
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PMID:Prostaglandin synthesis in aorta of atherosclerosis susceptible and atherosclerosis resistant pigeons. 742 65

Microsomes prepared from the brachial artery and the thoracic aorta of atherosclerosis resistant (AR) Show Racer and atherosclerosis prone (AS) White Carneau pigeons were incubated with 14C-prostaglandin endoperoxide (PGH) and prostaglandin products analyzed. The microsomes demonstrated minimal prostacyclin (PGI2) synthetase activity; 6-keto-PGF1 alpha (the hydrolytic breakdown product of PGI2) accounting for less than 2% of total products. Reduced glutathione enhanced PGE2 formation in both the AR and AS preparations identifying an active PGH-PGE isomerase. The AR preparations demonstrated increased PGH-PGE formation with age, reaching maximal activity at 8-9 months, then decreasing at 14 months. The AS group also demonstrated a similar pattern of enzyme activity. These studies indicate that a) unlike the mammalian preparations prostacyclin synthetase does not appear to be a major enzymatic activity of the pigeon aorta, rather, b) PGH-PGE isomerase is the major endoperoxide metabolizing activity in the pigeon aorta and thus, c) a deficiency of prostacyclin production is not involved in the geneis of atherosclerosis in the pigeon.
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PMID:Prostaglandin E2 synthesis in pigeon aorta: comparison of atherosclerosis-resistant (Show Racer) and atherosclerosis-prone (White Carneau) breeds. 742 66

The effects of single dose of PGE2 combined with vitamin E and with estradiol on experimental atherosclerosis were studied by means of morphological, ultrastructural, autoradiographic and several functional techniques. The results showed that two combined treatment groups had more coordinative inhibition on aortic and coronary atherosclerotic lesions, as well as on platelet aggregation, smooth muscle cell proliferation and lipid peroxidation than that of single dose of PGE2. It was revealed that the coordinative mechanism might be closely related to the synergistic inhibitory function of above-mentioned drugs on endothelial permeability, platelet aggregation, smooth muscle cell proliferation and lipid peroxidation.
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PMID:Experimental study on antiatherosclerotic treatment by PGE2 combined with vitamin E and estradiol. 771 36

Abnormal smooth muscle cell (SMC) proliferation is observed in several pathological situations such as atherosclerosis, pulmonary hypertension, and venous pathologies, resulting in a thickening of the vessel wall. If endothelial cells have been assumed to play a role in the triggering of this proliferation, no direct evidence is available. As ischemia is often linked to these situations, we exposed human umbilical vein endothelial cells (HUVEC) to hypoxia. The HUVEC-conditioned medium was then added to SMC and the proliferation of these cells was measured. We observed a pro-proliferative activity for SMC of the hypoxic HUVEC-conditioned medium but not of the normoxic HUVEC one. This pro-proliferative activity could not be inhibited if HUVEC were treated with cycloheximide but was blocked if the synthesis of prostaglandins by HUVEC was inhibited during hypoxia. PGD2, and especially PGF2 alpha at the concentration found in the hypoxic HUVEC-conditioned medium, were demonstrated to have a mitogenic effect on SMC. PGE2 also showed a pro-proliferative activity but at higher concentrations. In addition, the kinetics of increase in SMC proliferation induced by a mixture of the four prostaglandins at the corresponding concentrations was the same as the one observed with hypoxic HUVEC-conditioned medium. However, when tested on fibroblasts which do not respond to PGF2 alpha, hypoxic HUVEC-conditioned medium also had a pro-proliferative activity. In addition, anti-bFGF antibodies but not anti-PDGF blocked the mitogenic activity of this conditioned medium for SMC. Finally, the mitogenic effects of PGF2 alpha and of bFGF on SMC are additive. These results indicate that bFGF is probably also involved. These results indicate that these prostaglandins act in synergy with bFGF and are the molecules responsible for the pro-proliferative activity observed in hypoxic HUVEC-conditioned medium. We propose that these findings can explain the excessive growth of SMC in blood vessels following chronic ischemic situations.
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PMID:Hypoxia stimulates human endothelial cells to release smooth muscle cell mitogens: role of prostaglandins and bFGF. 802 Jun 5

Fifty-five patients with ischemic heart disease, familial hyperlipoproteinemia type IIb and essential hypertension kept anti-atherosclerosis diet incorporating 20 g of ichthyenic oil for 4 weeks. The diet resulted in positive shifts in clinical manifestations, a fall in blood levels of total cholesterol, triglycerides, atherogenic coefficient. The clotting time and duration of hemorrhage proved longer. As to fatty acid composition of red cell and platelet membranes, proportion of omega-6 reduced, while the share of omega-3 rose. This may underly inhibited synthesis of PGE2 and PGF2 alpha noted in the examinees.
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PMID:[Clinico-metabolic effects of fish oil in patients with ischemic heart disease, familial hyperlipoproteinemia and hypertension]. 804 6

It is our central hypothesis that periodontal diseases, which are chronic Gram-negative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2, IL-1 beta, PGE2, and TNF-alpha) which serve to initiate and exacerbate atherogenesis and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease.
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PMID:Periodontal disease and cardiovascular disease. 891 Aug 31

Injury of endothelial cells (EC) has been postulated as the initial trigger of the progression of atherosclerosis in patients with diabetes mellitus. We previously reported that decrease in a novel endothelium-specific growth factor, hepatocyte growth factor (HGF), by high D-glucose might be a trigger of endothelial injury. However, the physiological role of the local vascular HGF system has not yet been clarified. To investigate the role of HGF in endothelial injury, we initially examined the effects of HGF on endothelial injury induced by serum deprivation. Decrease in EC number by serum deprivation was significantly attenuated by addition of HGF as well as recombinant basic fibroblast growth factor, whereas vascular endothelial growth factor showed no effect. Apoptotic changes in EC induced by serum deprivation were also significantly attenuated by addition of HGF (p < 0.01). Given the protective action of HGF, we next studied the physiological role of local HGF production in endothelial regulation. We focused on the protective actions of prostaglandin (PG) I2, PGE and a phosphodiesterase type 3 inhibitor (cilostazol) on endothelial injury by high glucose, since these agents are widely used in the treatment of peripheral arterial disease which is frequently observed in diabetic patients. Treatment of human aortic EC with PGE1, PGE2, and a PGI2 analogue (beraprost sodium) as well as cilostazol stimulated EC growth. HGF concentration in conditioned medium from EC treated with PGE1, PGE2 or PGI2 analogue as well as cilostazol was significantly higher than that with vehicle (p < 0.01). Interestingly, treatment with PGI2 analogue or cilostazol attenuated high D-glucose-induced EC death, which was abolished by neutralizing anti-HGF antibody. Moreover, decreased local HGF production by high D-glucose was also significantly attenuated by PGI2 analogue or cilostazol. Finally, we tested the effects of PGE, PGI2 analogue and cilostazol on local HGF production in human aortic vascular smooth muscle cells (VSMC). Although high D-glucose treatment resulted in a significant increase in VSMC number, PGI2 analogue and/or cilostazol treatment had no effects on VSMC growth. However, the decrease in local HGF production by high D-glucose was significantly attenuated by addition of PGI2 analogue or cilostazol. Overall, this study demonstrated that treatment with PGE, PGI2 analogue or cilostazol prevented aortic EC death induced by high D-glucose, probably through the activation of local HGF production. Increased local vascular HGF production by prostaglandins and cilostazol may prevent endothelial injury, potentially resulting in the improvement of peripheral arterial disease.
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PMID:Role of hepatocyte growth factor in endothelial regulation: prevention of high D-glucose-induced endothelial cell death by prostaglandins and phosphodiesterase type 3 inhibitor. 930 Feb 42

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

Epidemiological, clinical, and experimental studies have demonstrated that high density lipoproteins (HDL) are protective against atherosclerosis. However, the respective influence of two main HDL subfractions (HDL2 and HDL3) on atherosclerosis process is not yet clear. The present study was designed to determine, which HDL subfraction was antiatherogenic in terms of eicosanoid release by human umbilical vein endothelial cells (HUVEC). Endothelial cells were incubated for 4 hours with HDL2 or HDL3 and prostaglandins 6-keto-PGF1alpha, thromboxane B2 and prostaglandin E2 were measured by RIA in culture supernatant. HDL2 has a dose dependent stimulatory effect on 6-keto-PGF1alpha release without stimulatory effect on thromboxane B2 secretion. The 6-keto-PGF1alpha/thromboxane B2 ratio increased progressively from 1.65 to 4.65 for 0.39 to 6.25 mg HDL protein/ml. The pattern of prostanoid secretion under influence of HDL3 showed a predominant response in 6-keto-PGF1alpha and TxB2 release. As regards PGE2, both HDL subfractions stimulated considerably secretion of this prostanoid in a dose dependent manner. In terms of PGI2/TxA2 balance the better antiatherogenic effect was observed with HDL2 subfraction.
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PMID:The effect of high density lipoprotein subfractions on endothelial eicosanoid secretion. 979 13


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