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

Platelets are involved in the progressive pathogenesis of atherosclerosis. It has been shown that there is usually an increase in platelet aggregation between 6 and 9 a.m.; in the present study. in 10 patients suffering from chronic occlusive arterial disease, the impedancemetric method was used to evaluate, in whole blood, platelet aggregation induced by ADP and collagen the day prior to and the day following the evening administration of 300 mg picotamide. Analysis of the data obtained shows, in accordance with the findings of other authors, in increase of platelet aggregation from 6 a.m. to 9 a.m. This increase is suppressed by the evening administration of the anti-aggregant.
 ...
PMID:[Changes in morning platelet aggregation in patients with peripheral obliterating arteriopathy after evening administration of picotamide]. 182 69

The effects of the intravenous administration of 100 mg of trapidil on systolic and diastolic left ventricular functions and coronary sinus blood flow, as well as on myocardial lactate metabolism and platelet aggregation, were investigated before and after pacing in 12 patients with coronary artery disease. Pacing without administration of trapidil provoked angina in 6 of these patients. During rest, trapidil decreased the mean blood pressure by an average of 5 mmHg (from 112 +/- 15 to 107 +/- 8 mmHg, p less than 0.05) and the left ventricular end-diastolic pressure by an average of 4 mmHg (from 10 +/- 3 to 6 +/- 2 mmHg, p less than 0.05). Trapidil also caused both the max dp/dt and the coronary sinus blood flow to increase slightly, although it had no significant effect on diastolic function, myocardial lactate metabolism, or platelet aggregation. During the pacing that followed trapidil administration, chest pain was not provoked in the same 6 patients who had previously experienced chest pain on pacing. The extent of ST-segment depression also improved from -1.6 +/- 0.3 to -0.9 +/- 0.7 mm (p less than 0.05) and there was a significant suppression of the production of myocardial lactate. When pacing was terminated, trapidil caused a decrease in left ventricular systolic pressure from 173 to 156 mmHg (p less than 0.05), and also caused a decrease of the left ventricular end-diastolic pressure, from 16 +/- 4 to 8 +/- 2 mmHg (p less than 0.05). Trapidil had no significant effect on platelet aggregation activity with either a 1 microM or a 2 microM dose of ADP (adenosine diphosphate). However, the beta-TG level was suppressed, decreasing from 119 +/- 14 to 99 +/- 19 ng/ml in the arterial blood (p less than 0.1) and from 114 +/- 9 to 103 +/- 17 ng/ml (p less than 0.1) in the coronary sinus blood. Reductions in the preload and afterload by trapidil were of far greater magnitude than either its coronary dilatory or positive chronotropic effects in patients with coronary artery disease. Thus trapidil, a new antianginal agent appears to inhibit the production of platelet derived growth factors and may, therefore, protect the arteries from atherosclerosis as it promotes beneficial systemic hemodynamics in patients with depressed ventricular function.
 ...
PMID:The effects of trapidil on left ventricular function and platelet aggregation in patients with coronary artery disease subjected to pacing. 183 67

There is considerable evidence from previous studies that platelets play an important role in the development and progression of atherosclerosis in hypertension, more so in relation to the stage of hypertension. Seventy one hypertensive patients (WHO stage I: 39, stage II: 23, stage III: 9) aged 19-84 (mean age: 56, 59 and 62 respectively for each stage) and 37 normal controls (aged 22-72 with a mean age of 52) were involved in this study. Hematocrit, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), beta-TG/PF4 ratio, total cholesterol (TC), low density lipoprotein-C, and triglycerides were higher in the hypertensive group while platelet count, circulating platelet aggregates, and high density lipoprotein-C were higher in the normotensive group. Among the hypertensives, stage III patients showed the highest beta-TG, PF4, beta-TG/PF4 ratio, triglycerides, and stage I with the least elevation. There were no significant differences noted in the ADP or epinephrine-induced platelet aggregation in both the normal and hypertensive patients. Other parameters such as heart rate, serum sodium, potassium, renal and liver function tests, plasma renin activity, aldosterone, fibrinogen thromboxane B2 and 6-Keto-PGF1 alpha, showed no significant differences in both groups. This study clearly showed that beta-TG/PF4 ratio and triglycerides are closely related to the stage of hypertension and are good indicators of in vivo platelet activation in hypertensives which may account for the acceleration of hypertensive vascular complications secondary to atherogenesis.
 ...
PMID:Relationship of platelet specific proteins and other factors to atherosclerosis in various stages of hypertension. 183 85

Hypercholesterolemia (mean plasma cholesterol: 15 mM) was induced in rabbits by the feeding of a chow diet enriched with a low amount (0.25%, w/w) of cholesterol only. Platelet size and protein content decreased significantly, but the whole blood platelet count did not change. The platelets became enriched in cholesterol, as indicated by a significant increase in the cholesterol:phospholipid molar (C/P) ratio. Specific responses of washed platelets stimulated with various agonists were studied to determine the effects of hypercholesterolemia on the various pathways of platelet aggregation in the absence of plasma components. In platelets from hypercholesterolemic rabbits compared with controls: aggregation induced by ADP was not altered; collagen-induced responses (aggregation, secretion of [14C]serotonin from prelabelled platelets, thromboxane A2 (TXA2) formation, mobilization of [3H]arachidonate from prelabelled platelets) were enhanced; with aspirin-treated platelets, aggregation induced by the TXA2 mimetic U46619 was enhanced: and thrombin-induced responses of both untreated platelets (aggregation, secretion of granule contents, TXA2 formation) and aspirin-treated platelets (aggregation) were enhanced. Thus, platelets from cholesterol-fed rabbits not only form more TXA2, but they aggregate more extensively when stimulated by its mimetic. In addition, it has not been previously recognized that these platelets are also hypersensitive to thrombin-induced aggregation that is independent of TXA2.
Atherosclerosis 1991 May
PMID:Platelet hypersensitivity in cholesterol-fed rabbits: enhancement of thromboxane A2-dependent and thrombin-induced, thromboxane A2-independent platelet responses. 187 12

The study was undertaken in normal and vasectomized monkeys to elucidate the relationship of circulating immune complexes and platelet aggregability with experimental aortic and coronary atherosclerosis. Four groups of animals, viz. sham-vasectomized stock diet fed, vasectomized stock diet fed, sham-vasectomized atherogenic diet fed, were studied for a period of 1 year. An increased incidence of atherosclerosis was noted with high levels of circulating immune complexes in vasectomized monkeys. Platelets obtained from atherogenic diet fed monkeys had a clear tendency of increased aggregation and agglutination in the presence of ADP, epinephrine and ristocetin respectively. Vasectomy produced a significant enhancement in platelet aggregation response with ADP and epinephrine in atherogenic diet fed animals. The aortic and coronary atherosclerosis was also significantly increased in atherogenic diet fed groups both with and without vasectomy.
 ...
PMID:Role of circulating immune complexes and platelet aggregation in the development of experimentally induced atherosclerosis in monkeys with normal intact vas deferens and following vasectomy. 189 99

Pertussis toxin, an irreversible inhibitor of some G proteins, inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. In the present study, the effects of the toxin were examined on endothelium-dependent and -independent relaxations of hypercholesterolemic and atherosclerotic porcine coronary arteries to assess the functional state of the endothelial pertussis toxin-sensitive G protein. Male Yorkshire pigs were maintained on either a regular diet (control group, n = 7) or a 2% high-cholesterol diet (cholesterol-fed group, n = 7) for 10 weeks. After the initial 2 weeks of maintenance, animals in both groups underwent balloon catheter removal of the endothelium of the left anterior descending or left circumflex coronary arteries. Endothelium-dependent responses were examined in vitro after 10 weeks of maintenance; at this time, a full lining of endothelial cells in both left coronary arteries was confirmed histologically. In arteries with endothelium of the control group (normal responses), pertussis toxin significantly inhibited the endothelium-dependent relaxations to serotonin, UK14304 (a selective alpha 2-adrenergic receptor agonist), and thrombin but not those to ADP, bradykinin, or the calcium ionophore A23187. In previously denuded arteries of the control group (effects of endothelial regeneration alone) or intact arteries of the cholesterol-fed group (effects of hypercholesterolemia alone), the relaxations to serotonin, UK14304, and thrombin were impaired significantly; those relaxations were impaired further in previously denuded arteries of the cholesterol-fed group (effects of atherosclerosis). The inhibitory effects of pertussis toxin were significantly reduced after endothelial regeneration and in hypercholesterolemia and were almost absent in atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Loss of endothelial pertussis toxin-sensitive G protein function in atherosclerotic porcine coronary arteries. 199 83

In addition to preserving the permselectivity of the vascular wall and providing an antithrombogenic surface, the vascular endothelium contributes importantly to the regulation of vasomotor tone. Indeed, the endothelium participates in the conversion of angiotensin I to angiotensin II; the enzymatic inactivation of several plasma constituents such as bradykinin, norepinephrine, serotonin, and ADP; and the synthesis and release of vasodilator substances such as prostacyclin and the recently discovered endothelium-derived relaxing factor (EDRF). The diffusible EDRF released from the endothelium is nitric oxide or a substance closely related to it such as nitrosothiol. The endothelium also synthesizes and releases vasoconstrictive factors, including products derived from arachidonic acid metabolism and the recently discovered peptide endothelin. An increasing body of evidence from experimental and clinical studies indicates that EDRF and endothelium-derived contracting factors play an important role in vascular physiology and pathology. It has become apparent that the balance of these factors may be a major determinant of systemic and regional hemodynamics. Moreover, through generally opposite effects on growth-related vascular changes, contracting factors such as endothelin and relaxing factors such as EDRF also may be important determinants of the vascular response to injury in various disease states such as atherosclerosis and hypertension. It is clear that the vascular endothelium is a complex and dynamic organ. Understanding endothelium function in normal physiology and disease states is of potential clinical importance and should be the focus of future investigation.
 ...
PMID:Role of endothelium-derived relaxing factor in regulation of vascular tone and remodeling. Update on humoral regulation of vascular tone. 204 72

Platelet aggregability was studied in 18 healthy volunteers during mental stress (a colour word test; CWT) and low- and high-dose adrenaline infusions using an ex vivo technique (filtragometry) and conventional in vitro aggregometry. CWT and high-dose adrenaline (3.4 nmol l-1 in plasma) shortened filtragometry readings, suggesting increased platelet aggregability in vivo. Low-dose adrenaline had no effect despite higher adrenaline levels in plasma (0.9 nmol l-1) than during CWT (0.4 nmol l-1). Platelet sensitivity to ADP in vitro was reduced following CWT and further reduced following adrenaline infusions. In vitro, adrenaline (50 nmol l-1) had little effect on platelet aggregation per se, but enhanced aggregability evoked by ADP (at ED50). Adrenaline potentiation of ADP-induced aggregation was enhanced after CWT, but was not related to filtragometry responsiveness to stress in vivo. Serum LDL-cholesterol levels were inversely correlated to filtragometry readings at rest, suggesting an adverse influence on platelet aggregability in vivo. HDL-cholesterol levels were inversely correlated to platelet sensitivity to ADP in vitro, suggesting a positive influence. Thus, sympatho-adrenal activation enhances platelet aggregability in vivo (as assessed by ex vivo filtragometry), but adrenaline alone cannot explain the pro-aggregatory effect of mental stress. Serum lipoprotein alterations associated with increased risk for atherosclerosis seem to enhance platelet aggregability. The conventional in vitro technique may poorly reflect platelet aggregability in vivo.
 ...
PMID:Platelet aggregability in humans: contrasting in vivo and in vitro findings during sympatho-adrenal activation and relationship to serum lipids. 212 99

A group of 22 subjects with type IIA hypercholesterolaemia (mean serum cholesterol = 8.3 +/- 0.3 mmol/l) were sex, age and weight matched with 22 control subjects (mean serum cholesterol = 4.5 +/- 0.1 mmol/l). Diastolic blood pressure was significantly higher in hypercholesterolaemic subjects (79.2 +/- 1.4 mm Hg) than in control subjects (71.9 +/- 1.4 mm Hg). While the high cholesterol group had 52% greater thromboxane production in clotted whole blood than controls this difference was not significant, and the platelet aggregation and serotonin secretion response to doses of collagen, ADP and arachidonic acid were similar between the 2 groups. Polymorphonuclear leukocyte (PMN) chemiluminescence (used as a measure of reactive oxygen species production) in response to low doses of the chemotactic-peptide FMLP and opsonized zymosan was significantly greater in high cholesterol subjects compared to their matched controls. The production of platelet activating factor (PAF) by calcium ionophore (2.5 micrograms) stimulated PMN isolated from hypercholesterolaemic subjects (11.5 +/- 1.4 ng/10(6) cells) was significantly greater than PAF production by cells from the control group (8.3 +/- 1.0 ng/10(6) cells). Leukotriene B4 release by PMN in response to calcium ionophore did not differ between the 2 groups. These data suggest a degree of leukocyte activation in hypercholesterolaemic subjects compared to controls with normal cholesterol. In addition, plasma levels of lyso-PAF were higher in high cholesterol subjects (317 +/- 21 ng/ml) compared to their matched controls (271 +/- 18 ng/ml) perhaps indicating increased plasma acetylhydrolase activity in subjects with raised cholesterol levels. Recently described biological activity for lyso PAF suggests a possible role for this substance in atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1990 Aug
PMID:Leukocyte and platelet function and eicosanoid production in subjects with hypercholesterolaemia. 217 12

To assess the effect of lovastatin on blood rheology, the hemorheological determinants fibrinogen, red cell aggregation, plasma viscosity, hematocrit and platelet aggregation (spontaneous and ADP-induced) were studied in 15 patients with type II hyperlipoproteinemia in the course of treatment with lovastatin. Prior to therapy, fibrinogen (Fgen), red cell aggregation (RCA-S, RCA-L) and plasma viscosity (PV) as well as cholesterol (Chol) and triglycerides (Tg) were increased in the hyperlipemic patients compared with healthy normolipemic controls (Fgen: 319.3 +/- 65 vs. 269.8 +/- 48 mg/dl; RCA-S: 7.93 +/- 1 vs. 6.62 +/- 1, RCA-L: 9.86 +/- 1 vs. 7.8 +/- 1 arbitrary units; PV: 1.75 vs. 1.63 mPa/s; Chol: 317.0 +/- 32 vs. 176.5 +/- 21 mg/dl; Tg: 154.5 +/- 88 vs. 72.8 +/- 16 mg/dl; all P less than 0.05). Three months of treatment with lovastatin resulted in a marked decrease in red cell aggregation and plasma viscosity, parallel to a fall in cholesterol (the following pretreatment values were monitored after a standard lipid-lowering diet; RCA-S: 7.59 +/- 1 vs. 6.65 +/- 0.9, RCA-L: 9.34 +/- 1 vs. 8.15 +/- 1 arbitrary units; PV: 1.74 vs. 1.65 mPa/s; Chol: 309.8 +/- 41 vs. 217.1 +/- 30 mg/dl; all P less than 0.01); fibrinogen however, remained unchanged throughout the treatment period (346.4 +/- 73.3 vs. 330.5 +/- 70.2 mg/dl, n.s.). No differences were seen in hematocrit and platelet aggregability between hyperlipemic patients and controls and no changes occurred in these parameters during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1990 Jul
PMID:Effect of lovastatin on hemorheology in type II hyperlipoproteinemia. 239 Jan 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>