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

The influence of red blood cells on spontaneous platelet aggregation (SPA) has been studied ex vivo. Platelet aggregation was quantified by measuring the fall in single platelet count using a new whole blood platelet counter. When aliquots of whole blood and autologous platelet rich plasma (PRP) were roller-mixed at 37 degrees C, a marked fall in platelet count occurred in whole blood due to SPA but platelet count remained almost unchanged in PRP. When blood from healthy young controls, aged 20-35 years, was compared with healthy old controls, aged 48-80 years, and patients with thrombotic complications, the extent of SPA was in the order: thrombotic patients greater than old controls greater than young controls. Prostacyclin and the new stable prostacyclin analogue Iloprost, at 8 nM effectively inhibited SPA. 2-Chloroadenosine (10 microM) which is an inhibitor of ADP-induced platelet aggregation was also an effective inhibitor of SPA. Acetylsalicylic acid (56 microM) and the thromboxane A2 receptor blocker BM13.177 (0.5 microM) only partially inhibited SPA. ADP from red blood cells is suspected to mediate red cell-induced SPA. However, the possibility that the red cells have an important physical role in SPA cannot be ruled out.
Atherosclerosis 1987 Aug
PMID:Red blood cells mediate spontaneous aggregation of platelets in whole blood. 244 48

The specific markers of platelet activation, e.g. platelet aggregation induced with ADP, AA and PAF as well as the levels of Beta-TG, TXB2, 6-keto-PGF1 alpha and cyclic AMP in the patients suffering from obliterative arteriosclerosis of the lower limbs were measured. It was found that these patients revealed hyperfunction of blood platelets expressed in increased sensitivity of platelets to ADP and PAF, increased levels of Beta-TG and TXB2 as well as decreased levels of 6-keto-PGF1 alpha and cyclic AMP. Obtained results support the concept that atherosclerosis consists of a wide-spread functional alteration of various types of cells.
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PMID:Blood platelet function in patients with obliterative arteriosclerosis of the lower limbs. 246 57

Vasoconstrictor responses are augmented in porcine coronary arteries in hypercholesterolemia and atherosclerosis, leading to an occurrence of coronary vasospasm in the latter condition. The role of the endothelium in the vascular hyperreactivity in hypercholesterolemic and atherosclerotic coronary arteries was examined, particularly in response to aggregating and related vasoactive substances. Male Yorkshire pigs underwent balloon endothelial denudation of the left anterior descending coronary artery (LAD) and 2% high-cholesterol feeding for 10 weeks. Electron microscopic examination demonstrated a full lining of endothelial cells in the LAD and the left circumflex coronary artery (LCX). Endothelium-dependent responses were examined in vitro. In cholesterol-fed animals, endothelium-dependent relaxations to aggregating platelets, serotonin, ADP, bradykinin, thrombin, and the calcium ionophore A23187 were depressed in LAD (atherosclerosis), while the relaxations to aggregating platelets, serotonin and ADP were depressed in LCX (hypercholesterolemia). Serotonin-induced contractions were endothelium-dependently augmented in atherosclerotic LAD; the endothelium-dependent component of the contractions was inhibited by blockers of cyclooxygenase. Bioassay studies demonstrated a depressed release of endothelium-derived relaxing factor(s) from the atherosclerotic LAD in response to serotonin. These experiments indicate that the endothelium-dependent relaxations to aggregating platelets and related vasoactive substances are severely impaired in atherosclerosis and moderately impaired in hypercholesterolemia. Since coronary atherosclerosis was induced by a combination of balloon endothelial injury (and regeneration) and high-cholesterol feeding in this study, the combined effects of those factors must account for the severely impaired responses in atherosclerosis. The depressed release of the endothelium-derived relaxing factor(s) and the concomitant release of vasoconstrictor product(s) of cyclooxygenase appear to be responsible for the impaired relaxations.
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PMID:Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis. 249 69

The effect of chronic oral defibrotide on platelet function, vascular PGI2 generation, atherosclerotic plaque formation and serum lipids was studied in rabbits. The animals were fed for 4 months a standard laboratory diet (150 g/day) with or without defibrotide (60 mg/kg/day) or a cholesterol-rich (1%) diet with or without defibrotide. Defibrotide significantly reduced the platelet reactivity ex vivo against collagen and ADP. This included a reduced aggregation response, thromboxane release and ATP secretion. Furthermore, the inhibition of platelet function and stimulation of platelet cAMP by iloprost, were significantly improved by defibrotide treatment. This was associated with an increased number of prostacyclin binding sites and enhanced PGI2 affinity in platelet membranes from these animals. Bradykinin stimulated PGI2 generation of segments of the thoracic aorta about 2-fold above control in both normo- and hypercholesterolemic rabbits. There was no difference in basal values between these groups but a more than 2-fold increase in either group by defibrotide treatment. Atherosclerotic plaque formation, determined by a subjective score, was found to be significantly reduced by defibrotide although the compound did not alter serum cholesterol levels. The data suggest potent and potentially valuable antiatherosclerotic effects of oral defibrotide: (i) normalization of platelet function by reduction of platelet hyperreactivity and improvement of the sensitivity towards prostacyclin, and (ii) stimulation of vascular PGI2 production.
Atherosclerosis 1989 Nov
PMID:Stimulation of vascular prostacyclin and inhibition of platelet function by oral defibrotide in cholesterol-fed rabbits. 251 13

Two of the many mediators synthesized by vascular endothelial cells (EC), are involved in maintaining the surface of the normal, healthy endothelium in a non-thrombogenic state. The first is prostacyclin, a product of arachidonic acid metabolism, discovered in 1976. This labile prostanoid, with a half life of approximately 3 minutes, relaxes vascular smooth muscle and inhibits the aggregation of blood platelets. Prostacyclin and its analogues are currently being tested in the clinic for cardiovascular diseases such as primary pulmonary hypertension. A number of drugs including defibrotide, nafazatrom, ronicol and cicletanine may exert their therapeutic effects by releasing prostacyclin from the EC. The second mediator discussed is endothelium-derived relaxing factor (EDRF), discovered in 1980, which also relaxes smooth muscle and inhibits the aggregation and adhesion of platelets. Substances which stimulate release of EDRF include acetylcholine, bradykinin and ADP. EDRF is even more labile than prostacyclin with a half life counted in seconds. It has recently been identified as nitric oxide formed from L-arginine by an unknown mechanism. Prostacyclin and EDRF are released together following stimulation of endothelial receptors and synergize to inhibit platelet aggregation. It is suggested that these mediators form the endothelial defence mechanism against blood-borne cells and chemicals and that breakdown of this barrier results in diseases such as hypertension and atherosclerosis. The peptide, endothelin is the third mediator under discussion. Characterised and synthesised in 1988, it is the most potent vasoconstrictor so far discovered. Three isomers of endothelin have been identified. Paradoxically, endothelin strongly releases both prostacyclin and EDRF thus modulating its own vasoconstrictor actions.
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PMID:Vasoactive mediators derived from the endothelium. 251 50

In a multi-center, double-blind, placebo-controlled trial in claudicating patients with peripheral atherosclerosis, the effects of 1 year of treatment with ketanserin (20 mg t.i.d. for 1 month, 40 mg t.i.d. thereafter; n = 63 patients) or placebo (n = 84 patients) on platelet function (aggregation in P.R.P. by 5-HT 5 x 10(-6) M, ADP 1 to 5 x 10(-6) M, collagen 2 micrograms/ml; platelet 5-HT content; plasma beta TG- and PF4-levels; serum TXB2) were analyzed. Before treatment, claudicating patients (n = 173) displayed an higher reactivity of platelets to 5-HT and signs of platelet activation/release in vivo (higher plasma beta TG-PF4, lower platelet 5-HT content and decreased platelet aggregation by ADP, collagen) in comparison with healthy controls (n = 50). After 1 year of treatment with ketanserin, but not with placebo, platelet aggregation induced by 5-HT (slope -41.1%) and platelet 5-HT content (-23.7%) were significantly reduced. PF4 and beta TG were significantly higher than their pre-medication values in the two trial groups. The other platelet function tests were not significantly modified by the treatment. Only the small subgroup of patients with initially elevated plasma beta TG levels (greater than 20 ng/ml) also scrutinized for hidden NSAID consumption or technical bias (exclusion of data with serum TXB2 less than or equal to 10000 pg/100 microliters and/or plasma PF4 greater than 10 ng/ml) had significantly lower plasma beta TG levels (-22.7%) than the pre-medication values after treatment with ketanserin, but not with placebo. The present study confirms that ketanserin affects some platelet functions, during long-term administration in claudicating patients with atherosclerosis.
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PMID:Platelet function during long-term treatment with ketanserin of claudicating patients with peripheral atherosclerosis. A multi-center, double-blind, placebo-controlled trial. The PACK Trial Group. 252 41

Atherosclerosis was induced in 13 Yorkshire pigs (4 weeks; 7-10 kg) by endothelial balloon denudation of the aorta and left anterior descending coronary artery and a diet containing 2% (wt/wt) of cholesterol, 8% (wt/wt) of lard fat and 0.5% (wt/wt) of bile acids. After 8 months 7 animals (group I) were sacrificed to determine the extent to which atherosclerosis had developed. The other 6 animals (group R) received a diet (no cholesterol, 5% (wt/wt) of lard fat and 5% (wt/wt) of fish oil) for 4 months. In I plasma cholesterol increased from 2.29 to 9.02 mmol l-1 after 8 months and in R it returned to 1.89 mmol l-1 after 12 months. Less marked changes occurred in plasma HDL cholesterol and triglycerides. ADP-induced platelet aggregation and the number of platelets remained constant in I whereas both parameters were reduced in R after 12 months. In the lesions of the abdominal aorta of I, cholesterol, cholesterol ester, phospholipid and triglyceride contents were 4.97, 2.08, 4.20 and 0.77 micrograms g-1 wet wt, respectively, whereas in R these values (3.02, 0.47, 2.70 and 0.44 micrograms g-1 wet wt, respectively), were close to the values measured in non-abraded vessel wall specimens. The Sudan IV-positive area of the aorta was 34 +/- 9% in I and 10 +/- 4% in R (P less than 0.05). Luminal encroachment of the denudated left anterior descending coronary artery was 11 +/- 3% in I and 13 +/- 3% in R (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of n-3 fatty acids on the regression of atherosclerosis in coronary arteries and the aorta of the pig. 262 Jun 86

The influence of varying dietary fatty acid ratios on plasma lipids, platelet function and the potential for thrombosis was evaluated in the African green monkey (Cercopithecus aethiops), an animal model widely used in cardiovascular research. Ten adult animals, 5 males and 5 females, at intervals of 2 months, were fed a series of 7 diets with fatty acid ratios (P:S) ranging from 3:1 to 1:4. Platelet aggregation in vitro, plasma levels of beta-thromboglobulin and platelet factor 4, platelet membrane fatty acid composition and plasma lipids including total cholesterol, HDL and LDL were monitored at the end of each dietary period. Platelet hypersensitivity to ADP aggregation (3 and 10 microM) and plasma beta-thromboglobulin were elevated in both males and females when dietary P:S exceeded 1.5:1 (beta-TG = 45 ng/ml) as compared to control diets either reflecting current North American or that recommended as a desirable dietary goal (P:S = 1:1, beta-TG = 10 ng/ml). Diets enriched in saturated fatty acids (P:S = 1:2) also altered platelet function, but the effects were most consistently observed in female animals (beta-TG = 32 ng/ml). Platelet hypersensitivity was lost and beta-TG levels were at baseline when the animals were returned to the control diets. Platelet sensitivity did not correlate with membrane composition which generally reflected dietary composition. Both the saturated and the polyunsaturated fatty acid enriched diets lowered plasma HDL levels, and the saturated fatty acid diets elevated plasma LDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1989 Jun
PMID:Effects of varying dietary fatty acid ratios on plasma lipids and platelet function in the African green monkey. 231 Apr 31

Platelets are involved in the progression of coronary atherosclerosis as well as in the development of the acute precipitating event. Recently, it has been shown that normal subjects present increased platelet aggregation between 6.00 a.m. and 9.00 a.m.; epidemiological studies have shown a higher incidence of myocardial infarction between these times. This study evaluated, by an impedence method using whole blood, platelet aggregation induced by ADP (3 microM) and collagen (2 microM/ml). Measurements were made at 6.00 a.m., 9.00 a.m. and 12.00 noon, the day before and the day after evening administration of 200 mg indobufen, a platelet aggregation inhibitor, in 12 patients with ischaemic heart disease. Patients showed a significant increase of platelet aggregation between 6.00 a.m. and 9.00 a.m. which was inhibited by the prior evening administration of indobufen.
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PMID:Effect of indobufen on whole blood platelet aggregation recorded in the morning in patients with ischaemic heart disease. 279 57

In 35 pigs atherosclerosis was induced by balloon abrasion and a diet containing 2% (w/w) cholesterol and 7% (w/w) lard fat. After 4 months of induction nine animals were killed (I) for analysis of the extent of atherosclerosis, while the diet of the other 26 pigs was changed to a low cholesterol diet containing either 9% (w/w) lard fat (L), 9% (w/w) fish oil (F) or 4.5% (w/w) lard fat and 4.5% (w/w) fish oil (LF). This diet was continued for 3 months to induce regression of atherosclerosis. The cholesterol-rich diet increased plasma total cholesterol, but did not affect plasma triglycerides. Low-cholesterol feeding decreased plasma total cholesterol in all three groups, but triglycerides only in LF and F. Lipid infiltration of the aortic wall was similar in I, L, LF and F. In the denudated coronary arteries of I mean luminal encroachment was 11 +/- 2%. This was similar in L (13 +/- 4%) but significantly lower (P less than 0.05) in LF (6 +/- 2%) and in F (3 +/- 1%). In the non-abraded coronary arteries of I mean luminal encroachment was 1.3 +/- 0.3%. For F and LF similar values were found, but in L there was an increase to 11 +/- 3% during low-cholesterol feeding. ADP-induced platelet aggregation was lower in LF and F than in L. Thromboxane A2 production was only reduced in F, while the production of the weak thromboxane A3 agonist was larger in F than in LF. It is concluded that fish oil retards the progression of and causes regression of coronary atherosclerosis.
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PMID:Mackerel oil and atherosclerosis in pigs. 280 83


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