Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Effects of co-dergocrine mesylate (Hydergine), a drug widely used for the therapy of cerebral vascular disease on local platelet accumulation in the carotid artery region was studied by means of the platelet uptake ratio (PUR) and on the systemic platelet-vascular wall interaction as calculated from platelet half-life were investigated. A placebo controlled, double blind, randomised protocol was used, 18 patients were treated with co-dergocrine and compared to placebo (n = 18). Co-dergocrine treatment resulted in a significant decrease in platelet deposition, PUR decreased from 1.28 +/- 0.05 before treatment to 1.25 +/- 0.06 on day 5 of therapy with a statistically significant (p less than 0.001) in the paired comparison. In the control group the corresponding changes from 1.29 +/- 0.04 before to 1.28 +/- 0.04 did not show a p-value of less than 0.05 in paired comparison. Platelet half-life (72 +/- 11 before vs. 76 +/- 11 hours after 5 days of co-dergocrine treatment) showed a statistically significant (p less than 0.001) prolongation, whereas in the placebo group no relevant change of T/2 was observed (71 +/- 10 before vs. 72 +/- 10 hours on day 5, p greater than 0.10). No relevant effects on ADP-induced platelet aggregation, platelet-release reaction, platelet aggregate ratio, TXB2 plasma levels and thrombin-induced MDA-formation could be detected. These results indicate that co-dergocrine decreased in-vivo platelet residence time to atherosclerotic lesions of the carotid artery. Co-dergocrine may thereby be of benefit in prevention of mural thrombus formation and prevention of transient ischemic attacks, but also of atherosclerosis in man.
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PMID:Effects of Hydergine on platelet deposition on "active" human carotid artery lesions and platelet function. 281 44

PAF-acether, a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms of action of PAF are largely unknown. We have found that the psychotropic triazolobenzodiazepine drugs, alprazolam and triazolam, potently (IC50 less than 1 microM) inhibit PAF-induced shape change, aggregation and secretion of human platelets. These effects are specific for PAF-activation, since the responses of human platelets to other agonists (ADP, thrombin, epinephrine, collagen, arachidonate and the Ca++ ionophore, A23187) are not inhibited by these triazolobenzodiazepines. The action of triazolobenzodiazepines on PAF-induced platelet function has clinical relevance, especially in diseases where enhanced platelet aggregability may lead to thrombosis and atherosclerosis. In addition, the ability of triazolobenzodiazepines to inhibit other PAF-mediated cellular-responses, such as anaphylactic shock or bronchoconstriction, suggests that these drugs may be useful in preventing several known pathophysiological effects of PAF. The specific antagonism of PAF action by psychotropic drugs also suggests that PAF or PAF-like phospholipids may play a role in neuronal function. This possibility was tested by examining the effects of PAF on neural cells of the clonal line NG108-15, grown in culture in a chemically defined, serum-free medium. Low concentrations of PAF (0.5-2.5 microM) induced neurite extension in NG108-15 cells, whereas higher concentrations (greater than 3 microM) were cytotoxic. Using NG108-15 cells preloaded with aequorin, it was found that PAF causes an increase in intracellular ionized calcium concentration, which is dependent on the presence of extracellular calcium. These results suggest that PAF-induced Ca++ uptake may play a role in neuronal development, and that circulating PAF may contribute to the neuronal degeneration caused by the exposure of neural tissues to blood in situations such as spinal cord injury, trauma, or stroke.
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PMID:Interactions of the alkyl-ether-phospholipid, platelet activating factor (PAF) with platelets, neural cells, and the psychotropic drugs triazolobenzodiazepines. 289 25

Platelets from rats with genetically determined hypercholesterolaemia are hypersensitive to aggregation induced by thrombin compared with platelets from their genetic controls without hypercholesterolaemia. Aggregation or release induced by thrombin of platelets from hypercholesterolaemic and control rats correlated significantly with plasma cholesterol concentrations. Platelet responses to ADP or collagen were not different between the groups. The hypersensitivity to thrombin-induced aggregation was independent of released ADP or products of arachidonic acid metabolism. The changes in platelet sensitivity occurred with only moderate increases in plasma cholesterol concentration and with no detectable changes in total platelet cholesterol. The hypersensitivity of platelets from hypercholesterolaemic rats was not associated with a reduction in platelet survival or any significant injury to the aortic endothelium in these animals. Platelets from hypercholesterolaemic rats were smaller than platelets from controls. Thus, platelets from rats with genetically determined hypercholesterolaemia have alterations in function similar to those found with platelets from rats with diet-induced hypercholesterolaemia indicating that this strain can be used to study the mechanisms by which cholesterol can change platelet function without the possible complicating effects of dietary factors. Since platelet hypersensitivity occurred in rats with genetically determined hypercholesterolaemia without a reduction in platelet survival, these studies are also consistent with the reduced platelet survival found in animals with diet-induced hypercholesterolaemia being independent of platelet changes.
Atherosclerosis 1989 Mar
PMID:Platelet function and survival in rats with genetically determined hypercholesterolaemia. 292 65

In order to investigate the effect of fish oil on intimal proliferation of coronary arteries with a fixed stenosis normolipidemic piglets received a basic diet to which either 9% (w/w) lard (L, n = 8) or 4.5% (w/w) lard and 4.5% (w/w) mackerel oil (ML, n = 8) was added for 4 months. Stenosis was applied by implanting a 4.0 X 2.0 mm (i.d.) Teflon constrictor around the left anterior descending coronary artery (LADCA) (o.d. 2.7 +/- 0.1 mm). During the dietary period ADP-induced platelet aggregation in whole blood was higher in L than in ML. Partial replacement of 20:4 n - 6 by 20:5 n - 3 fatty acids in the platelet membranes of ML may have altered platelet aggregation by changes in eicosanoid synthesis. The plasma cholesterol and triglyceride levels did not change in L, but decreased in ML. At the end of the 4-month dietary period the animals were again anesthetized and regional myocardial perfusion (radioactive labelled microspheres) and systolic segment length shortening (SLS) were measured while the hearts were paced at 160 pulses/min. Perfusion and SLS of non-LADCA nourished segment were similar for L and ML. However, transmural flow to the LADCA perfused myocardium was impaired in both groups, but the deficiency in endocardial perfusion was considerably larger in L than in ML, resulting in a larger loss of SLS in the former. Remote (2-3 cm from the site of the constrictor) luminal encroachment was minimal (less than 2%) in both groups, but at the site of the constrictor there was significant encroachment in both groups which was higher in L (62 +/- 7%) than in ML (11 +/- 4%). It is thought that in these normolipidemic pigs the reduction in platelet aggregation may play a role in the smaller intimal proliferation of the fish oil-fed animals.
Atherosclerosis 1989 Mar
PMID:Does platelet aggregation play a role in the reduction in localized intimal proliferation in normolipidemic pigs with fixed coronary artery stenosis fed dietary fish oil? 292 67

Serum lipoproteins, fatty acids in plasma lipid esters and in platelet phospholipids were assessed in 64 patients with ischaemic heart disease (IHD) and in 67 controls. Hyperlipoproteinemia (HLP) (VLDL triglycerides greater than 1.4 mmol/l and/or LDL cholesterol greater than 5.2 mmol/l) was found in 64% of the patients. In the plasma lipid esters the relative concentrations of saturated and monounsaturated fatty acids as well as dihomo-gammalinolenic acid were higher in the IHD patients whereas the linoleic acid concentrations were lower. The altered fatty acid pattern was apparent both in patients with and without HLP. In the platelet phospholipids there was a relative increase of oleic acid and a decrease of stearic acid. The relative content of eicosapentaenoic acid was slightly reduced whereas the linoleic acid concentrations were unchanged compared to the controls. Platelet aggregation induced by ADP and collagen was enhanced in the IHD patients. The lowest threshold value for ADP-induced aggregation was found in the normolipidemic patients. Since there were almost no differences in the relative contents of the long-chain polyunsaturated fatty acids in the platelet phospholipids between patients and controls it is concluded that mechanisms other than the prostaglandin-mediated pathway may contribute to the increased platelet aggregation in IHD patients.
Atherosclerosis 1985 Dec
PMID:Fatty acid composition of platelets and of plasma lipid esters in relation to platelet function in patients with ischaemic heart disease. 293 56


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