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

The in vitro effects of prostaglandins E1 and F1alpha on the activity of cholesteryl ester synthetase and cholesteryl ester hydrolase activities of the pigeon aorta were examined. It was found that prostaglandin E1 markedly inhibited the cholesteryl ester hydrolase activity in the supernatant fraction and slightly inhibited the cholesteryl ester synthetase activity. Prostaglandin F1alpha, however, modestly stimulated the cholesteryl ester hydrolase activity both in the microsomal and in the supernatant fraction of the aorta. These observations strongly warrant further studies on the role of prostaglandins in atherogenesis.
Atherosclerosis 1977 May
PMID:Effect of prostaglandins E1 and F1alpha on the activities of cholesteryl ester synthetase and cholesteryl ester hydrolases of pigeon aorta in vitro. 1 25

We studied the effects of glycated lipoproteins of low- and high-density (LDL and HDL) on platelets and vascular endothelial cells. After pretreatment for 5 minutes at 37 degrees C, the thrombin-induced synthesis of thromboxane B2 in washed platelets was significantly increased by glycated LDL as compared with native LDL (198.9 +/- 16.2 vs 90.3 +/- 29.4 ng/10(9) platelets, n = 8, p less than 0.01). Platelet aggregation was also increased by glycated LDL as compared with native LDL. After treatment with platelet-rich plasma for 5 hours at 37 degrees C, these values were suppressed by native HDL vs the control (buffer), but not by glycated HDL. Abnormalities in the release of 6-keto prostaglandin F1 alpha and lactate dehydrogenase from vascular endothelial cells were also induced by glycated LDL and/or HDL. These observations suggest that abnormalities induced in platelets and vascular endothelial cells by glycated lipoproteins may play an important role in the development of atherosclerosis in patients with diabetes mellitus.
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PMID:Abnormalities in platelets and vascular endothelial cells induced by glycated lipoproteins. 139 75

The present study evaluated indomethacin therapy--a nonsteroidal anti-inflammatory drug--on experimental hyperlipidemia and atherosclerosis in Rhesus monkeys. Twenty-four monkeys were divided randomly into four groups of six. Two groups received stock pellet diet and two were given an atherogenic diet for six months. After this period, one stock diet-fed group and one atherogenic diet-fed group were treated with oral indomethacin (2.5 mg) on alternate days for a further six months. Serum lipids and lipoproteins were markedly elevated in atherogenic diet-fed monkeys. Generally, indomethacin did not exert a hypocholesterolemic effect; however, liver cholesterol was decreased (P less than 0.05) in atherogenic diet-fed monkeys treated with indomethacin. High density lipoprotein cholesterol was increased in stock diet-fed, indomethacin-treated monkeys but not in atherogenic diet-fed, indomethacin-treated monkeys. Apoprotein A-I was not affected by indomethacin in either stock or atherogenic diet-fed monkeys; however, the drug produced a significant (P less than 0.01) reduction of serum thromboxane B2 in stock diet-fed monkeys, without restoring the 6-keto-prostaglandin F1 alpha to pretreatment levels. A protective role of the drug was noted on both the extent and severity of aortic and coronary atherosclerosis.
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PMID:Effect of indomethacin on serum lipids, lipoproteins, prostaglandins and the extent and severity of atherosclerosis in rhesus monkeys. 157 66

A study is presented of a 48-year-old female patient and her three siblings with familial hypercholesterolemia. The family members had episodes of cerebral infarction and apparently had atherosclerosis of the internal carotid artery, but no coronary heart disease due to their almost normal level of cholesterol. The laboratory studies of the family members revealed the elevations of serum lipid peroxides, serum lipoprotein(a), leukotriene C4 in blood, the thromboxane B2/6-keto-prostaglandin F1 alpha ratio in plasma and serum hydroxyl radical. Therefore, it is suspected that these factors accelerating atherosclerotic process caused the cerebral infarction. The patient demonstrated corneal opacities, palpebral xanthomas, thickened Achilles tendons, polyneuropathy and the carpal tunnel syndrome. Laboratory studies revealed an elevation in the OKT4/8 ratio, monocyte dysfunction with respect to phagocytosis and chemotaxis, and the presence of the 46XX/45XO mosaic chromosome. Lipid deposits were observed in the Achilles tendon, the transverse carpal ligament, the Schwann's cells and axons of the sural nerve, and in the keratocytes and stroma of the cornea. Following the administration of tocopherol nicotinate and probucol, the patient's serum lipid peroxide normalized and there was improvement in her palpebral xanthomas, thickening of the Achilles tendons and polyneuropathy. We conclude that the lipid deposits in this patient were due to the abnormal oxidative metabolism of low-density lipoprotein and a disturbance of the scavenger pathway due to the monocyte dysfunction.
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PMID:A family of familial hypercholesterolemia with cerebral infarction and without coronary heart disease. An unusual case with corneal opacity, polyneuropathy and carpal tunnel syndrome in the family: therapy with probucol and tocopherol nicotinate. 177 33

Recently, platelet factor 4 (PF4) release by heparin (heparin-releasable PF4) has been examined as a useful marker of the interaction between the substances liberated from circulating platelets and the vascular endothelium. We compared the plasma levels of PF4 and beta-thromboglobulin (beta-TG) after intravenous heparin injection in patients with coronary artery disease (CAD) and normal control subjects. We also studied the effects of low-dose aspirin (81 mg/day) on the plasma level of heparin-releasable PF4 in the CAD patients. Blood samples were obtained before and 5 min after the intravenous injection of heparin (1,000 IU) from 23 patients with CAD and 15 normal control subjects. Although the plasma beta-TG level remained unchanged after heparin injection, the plasma PF4 level markedly increased in both groups. There was a significant difference in plasma PF4 levels at 5 min after heparin injection between the CAD group (100.1 +/- 38.1) and the control group (61.0 +/- 24.0) (p less than 0.01). The PF4/beta-TG ratio after heparin injection was also higher in the CAD group than in the control group (p less than 0.01). There was a correlation between the PF4/beta-TG ratio after heparin and the Gensini CAD score, which defines the severity of coronary atherosclerosis (r = 0.489, n = 23, p less than 0.01). Low-dose aspirin was administered to 11 CAD patients for 246.0 +/- 28.8 days. Blood samples for the assay of PF4 and beta-TG were obtained as stated above, and platelet aggregation, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) levels were also measured before and during aspirin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin-releasable platelet factor 4 in patients with coronary artery disease. 154 Oct 73

We investigated the effects of neuropeptide Y on the prostacyclin production of cultured porcine aortic endothelial cells by measuring the stable metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha, by radioimmunoassay. Neuropeptide Y induced dose- and time-dependent stimulation of prostacyclin production by cultured porcine aortic endothelial cells. The lowest stimulatory concentration of neuropeptide Y was 10(-8) M and maximal response, a 2.8 fold rise, was obtained with 10(-6) M. The stimulation lasted at least 24 h. The effect was associated with the stimulation of arachidonic acid release. Our data suggest that neuropeptide Y may inhibit the development of atherosclerosis by stimulating prostacyclin synthesis.
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PMID:Neuropeptide Y stimulates prostacyclin production in porcine vascular endothelial cells. 188 60

Alterations in the synthesis of thromboxane A2 (TxA2) and prostacyclin have been implicated in the development of atherosclerosis. We measured the amounts of the degradation products of these substances, TxB2 and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), respectively, as well as PGE2, that were synthesized by slices and the luminal surfaces of aortas from rabbits fed either a control diet or a diet supplemented with cholesterol and peanut oil. For these studies, we developed conditions that were designed to minimize the autoinactivation of cyclooxygenase during removal and preparation of the tissue. Pretreatment of aortas with a medium containing ibuprofen and EDTA resulted in an approximately twofold increase in 6-oxo-PGF1 alpha production upon subsequent incubation. Despite the increased lipid peroxidation associated with atherosclerotic lesions, we observed no changes in either aortic 6-oxo-PGF1 alpha production or in the levels of its major urinary metabolite, 2,3-dinor-6-oxo-PGF1 alpha, after as long as 15 weeks of dietary supplementation with cholesterol and peanut oil. Similarly, synthesis of PGE2 by aortic slices and the aortic lumen was the same in cholesterol-fed and control rabbits. In contrast to aortic 6-oxo-PGF1 alpha and PGE2 synthesis, there was a dramatic 10-fold increase in TxB2 released from slices of thoracic aorta after 15 weeks on the atherogenic diet. This was much greater than the approximately twofold increase in the synthesis of TxB2 by the luminal surface of the thoracic aorta, suggesting that the primary site of TxB2 synthesis in the aorta is in the inner part of the blood vessel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis of prostaglandins and thromboxane B2 by cholesterol-fed rabbits. 190 62

Generation of thromboxane A2 (TxA2) and prostacyclin (PGI2) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine skin bleeding time was investigated in 7 patients with atherosclerosis (angiographically verified obstructions of the femoral arteries) and in 7 normal control subjects apparently free of atherosclerotic lesions. Similar amounts of TxA2 (measured as thromboxane B2, TxB2) were generated at the site of plug formation in the patients with peripheral vascular disease (PVD) and in the control subjects. Significantly lower levels of PGI2 (measured as 6-keto-prostaglandin F1 alpha, 6-keto-PGF1 alpha) were found in blood from an injury of the microvasculature in the patients compared with the controls. These data do not suggest a major role of the platelet prostaglandin metabolism in the development of atherosclerosis. However, decreased synthesis of PGI2 by endothelial cells might contribute to the development and/or progression of atherosclerotic lesions. In the patients with PVD, low-dose aspirin (50 mg/day for 7 days) resulted in a greater than 90% inhibition of the TxB2 production at the site of plug formation. Following low-dose aspirin 6-keto-PGF1 alpha levels were below 20 pg/ml (limit of sensitivity of our radioimmunoassay procedure) in the majority of the samples. We therefore conclude that in patients with PVD a decreased synthesis of PGI2 by endothelial cells might contribute to the progression of atherosclerosis. Furthermore, low-dose aspirin treatment results in a similar inhibition of the platelet prostaglandin generation as recently observed in healthy subjects.
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PMID:Thromboxane A2 and prostacyclin generation in the microvasculature of patients with atherosclerosis--effect of low-dose aspirin. 250 52

Glycosylation of low-density lipoprotein (LDL) is known to be increased in diabetic patients. Recent studies have demonstrated that glycosylated (glc-) LDL contributes to the acceleration of atherosclerosis in diabetes. In the present study, we evaluated the effect of glc-LDL prepared in vitro on platelet aggregation and thromboxane B2 (TxB2) production in washed human platelets and on 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) production by cultured bovine aortic endothelial cells. After preincubation of washed platelets with glc-LDL or control LDL, thrombin-induced platelet aggregation and TxB2 production were measured. Control LDL enhanced the platelet aggregation rate and TxB2 production in a time- and dose-dependent manner. Glc-LDL showed significantly greater enhancement of those platelet functions than control LDL. On the other hand, while 6-keto-PGF1 alpha production was stimulated by control LDL in a time- and dose-dependent manner, glc-LDL significantly reduced the stimulatory effect of control LDL on 6-keto-PGF1 alpha production. These results suggest that modification of prostaglandin synthesis in platelets and endothelial cells by glycosylated LDL may lead to platelet hyperaggregation and thrombus formation in diabetes.
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PMID:Modification of prostaglandin synthesis in washed human platelets and cultured bovine aortic endothelial cells by glycosylated low density lipoprotein. 263 93

Endothelial cell damage is considered to be the initial step in the genesis of thrombosis and atherosclerosis. Recently, the adhesion of erythrocytes from patients with diabetes or sickle cell anemia to endothelial cells was found to be increased and correlated with the severity of vascular complications. We have measured by radioimmunoassay the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) as an index of prostacyclin (PGI2) production, during red cell adhesion to endothelial cells in culture. The amount of 6-keto-PGF1 alpha released after incubation with normal red cells was similar to that observed with buffer (1.07 +/- 0.32 nmol/10(6) endothelial cells). However, after the adhesion of erythrocytes from patients with diabetes or sickle cell anemia, the amount of 6-keto-PGF1 alpha produced was significantly increased (P less than 0.01) and was correlated with the extent of erythrocyte adhesion (P less than 0.05). Tritium-labeled PGI2 was found to bind to erythrocytes, and the binding was time and concentration dependent. PGI2 release was inhibited by the cyclooxygenase inhibitor (flurbiprofen), whereas red cell adhesion remained unchanged. Fibrinogen potentiated erythrocyte adhesion and PGI2 production. The increase in PGI2 production after the adhesion of red cells from patients with diabetes or sickle cell anemia to endothelial cells indicates that endothelium may be damaged by abnormal erythrocyte adhesion.
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PMID:Release of prostacyclin after erythrocyte adhesion to cultured vascular endothelium. 308 70


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