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)

Activated platelets secrete from their alpha granules a protein-like factor which stimulates the uptake of oxidized low-density lipoprotein (Ox-LDL) by macrophages. The aim of the present study was to evaluate the effect of three purified proteins obtained from platelet alpha granules: platelet-derived growth factor (PDGF), platelet factor-4 (PF-4), and beta-thromboglobulin (B-TG), on the uptake of Ox-LDL by macrophages. Cellular degradation of Ox-LDL by the J-774 A.1 macrophage-like cell line, that was preincubated for 18 h at 37 degrees C, with increasing concentrations of partially purified PDGF, (designated PDGF-CMS-III) was increased by up to 36% in comparison to control cells preincubated without PDGF. This effect was due to PDGF-mediated increase in the number of macrophage receptors for Ox-LDL. The enhanced uptake of Ox-LDL by PDGF resulted in an increase in cellular cholesterol content. Preincubation of macrophages with two types of recombinant PDGF dimers (10 ng/ml), revealed that PDGF-BB stimulated Ox-LDL cellular degradation by 64%, whereas PDGF-AB demonstrated only 34% stimulation, in comparison to control cells that were not treated with PDGF. The stimulatory effect of PDGF-CMS-III and PDGF-AB were reduced by 20% and 28%, respectively, when incubated in the presence of H-7, a specific protein kinase C inhibitor. When macrophages were preincubated with B-TG, cellular uptake of Ox-LDL was reduced by up to 30% at 100 ng B-TG/ml. This effect, however, was obtained only when B-TG was present in the incubation medium. Cellular degradation of Ox-LDL was not affected by preincubation of the cells with PF-4. Pretreatment of PCM with anti-PDGF or anti-B-TG antibodies abolished the effects of PCM on Ox-LDL degradation by macrophages. PDGF, thus, may represent the protein-like factor present in PCM which stimulates Ox-LDL degradation by macrophages, whereas B-TG may have a role in the recognition of PCM particles by the macrophage scavenger receptor. Modulation of macrophage cholesterol content by proteins secreted from activated platelets may have an important role in foam cell formation and atherosclerosis.
 ...
PMID:Proteins derived from platelet alpha granules modulate the uptake of oxidized low density lipoprotein by macrophages. 138 28

Although intimal proliferation of smooth muscle cells (SMC) is recognized as one of the key mechanisms in the development of atherosclerosis, our knowledge of the role of circulating growth factors for SMC in this process is limited. In the present study the plasma levels of platelet-derived growth factor (PDGF), beta-thromboglobulin (beta-TG), platelet factor 4 (PF 4) and total growth factor activity were determined in a group of 30 young postinfarction patients who had participated in an angiographic study of mechanisms associated with progression of coronary atherosclerosis. Significant correlations were found between the total growth factor activity in plasma and progression (r = 0.42, P < 0.05), as well as severity (r = 0.52, P < 0.01), of global coronary atherosclerosis. Attempts to identify the nature of the total growth factor activity indicated that less than 20% could be attributed to PDGF, the major serum mitogen for SMC. PDGF levels determined by radioimmunoassay were not related to progression or severity of global coronary atherosclerosis, but showed a significant association with the number and severity of distinct stenoses (r = 0.40, P < 0.05). Due to the retrospective design of this study, it is not possible to conclude whether there is a causal relationship between circulating growth factors and development of coronary atherosclerosis.
 ...
PMID:Association between high levels of growth factors in plasma and progression of coronary atherosclerosis. 145 23

In order to evaluate whether plasma beta-thromboglobulin (as a marker of the degree of platelet function) in patients presenting clinically evident atherosclerosis is related to the presence or absence of different risk factors (smoking habit, arterial hypertension, hypercholesterolemia, diabetes, hypertriglyceridemia, obesity, hyperuricemia, alcoholism), 40 patients have been studied in whom mean beta-thromboglobulin levels was 54 +/- 25.56 ng/ml, which is very superior to levels considered normal. However, the presence of one or more risk factors did not lead to significant variations in b-thromboglobulin concentrations, and no differences were found either when each risk factor was considered separately. The positive correlation (r = 0.98; p less than 0.01) between beta-thromboglobulin and apo B levels is highlighted. The results suggest that platelet hyperfunction seems to be due to a greater extent to the atherosclerotic process rather than to the existence of a particular risk factor.
 ...
PMID:[Beta-thromboglobulin levels and atherosclerosis. Its relationship with the presence of risk factors]. 153 62

This study was conducted to investigate acute effects of smoking on platelet function, endothelial cells and plasma lipids and to follow these parameters after Aspirin ingestion. Twelve fasting smokers each inhaled the smoke of one cigarette. Blood was drawn before and 10 min after smoking. Plasma nicotine, measured by gas chromatography, increased from 13.48 before smoking to 78.41 nM after smoking. Platelet aggregation to thrombin and ADP increased significantly (P less than 0.001). The platelet aggregate ratio decreased from 0.95 to 0.75 (P less than 0.005). Plasma beta-thromboglobulin also increased in post-smoking samples as measured using radioimmunoassay. 'Circulating endothelial cells' increased significantly after smoking (P less than 0.005). Triglycerides decreased (P less than 0.005) in plasma and in the VLDL fraction (P less than 0.05). Both post-smoking plasma free fatty acids and free glycerol increased, respectively, as compared with respective values. Lipase activity ascribable to lipoprotein lipase and hepatic lipase, absent in pre-smoking plasma samples, could be detected in post-smoking plasma without heparin injection. At least 1 week later, the subjects returned to follow an identical protocol except that they had ingested Aspirin (650 mg) 10-14 h before blood sampling. The same parameters were measured before and after smoking the same cigarette. Except for plasma nicotine, all the smoking-induced changes were abolished by ingestion of Aspirin. The results of this study indicate an interrelationship between platelet hyperactivity, endothelial injury and plasma lipids. They also demonstrate an inhibition of the major smoking-induced changes by Aspirin in the presence of high plasma nicotine levels. It is concluded that Aspirin may offset several of the deleterious acute effects of smoking. However, our conclusions cannot be, in any way, extended for long-term effects of both smoking and Aspirin treatment. Based on these data, it is suggested that there may be some links between platelet hyperactivity, endothelium injury and plasma lipids.
Atherosclerosis 1992 Apr
PMID:Acute influence of smoking on platelet behaviour, endothelium and plasma lipids and normalization by aspirin. 146 56

The influence of a 4-weeks therapy with 500 mg ticlopidine daily on platelet function parameters was examined in 10 male healthy volunteers aged 20-33 years in order to extend the knowledge on the antiplatelet activity of this substance. Ticlopidine significantly (p less than 0.01) affected ex-vivo platelet aggregation induced by ADP and increased platelet sensitivity to the antiaggregatory action of PGI2. Generation of TXB2 from endogenous substrate during spontaneous clotting of blood (serum-TXB2), conversion of exogenous radiolabelled arachidonic acid into TXB2 and MDA-formation in isolated platelets were unaffected by the treatment. The TXB2-level in plasma of volunteers, however, was decreased, after administration of the drug. The diminished alpha-granule content liberation (beta-thromboglobulin: p less than 0.01; PDGF: p less than 0.01; PF4 not significant) indicates that ticlopidine induces a decrease in platelet activity. The beneficial effect on release reaction is not associated with a decrease in TXA2-formation. Our results demonstrate that ticlopidine inhibits platelet activity, especially the PDGF-release. These results confirm the value of this drug in the prevention of atherosclerosis and its thromboembolic complications.
 ...
PMID:Ticlopidine and platelet function in healthy volunteers. 161 96

Macrophages and monocytes have essential roles in normal wound healing, in the immune response, and in the pathogenesis of atherosclerosis. Platelet-derived growth factor (PDGF) stimulates the transcription of the early response gene, JE, and its human homolog, macrophage chemotactic protein-1 (MCP-1) in fibroblasts. JE/MCP-1 encodes a cytokine which is a member of a superfamily of small inducible genes that include platelet factor 4, beta-thromboglobulin, 310-C/NAP-1/IL-8, IP-10, KC/gro/MGSA, and others which may play important roles in the inflammatory and immune response. We now report that glucocorticoids inhibit the transcriptional induction of the JE gene by PDGF and serum in a dose-dependent manner. The glucocorticoid response followed the expected anti-inflammatory rank order of potency and was not due to a shift in the time course of induction. Nonsteroidal anti-inflammatory agents were ineffective in reducing JE mRNA levels. Dexamethasone inhibited the accumulation of JE transcripts induced by PDGF, 12-O-tetradecanoylphorbol-13-acetate, and double-stranded synthetic RNA. Nuclear runoff assays demonstrated that the negative regulation occurred by decreasing the transcriptional induction of the JE gene. No effects on JE message stability could be detected in the presence of dexamethasone. The protein synthesis inhibitors cycloheximide and puromycin reversed the glucocorticoid-mediated inhibition and suggested that new protein synthesis was necessary. These results suggest that the transcriptional inhibition of glucocorticoids is mediated by the expression of a labile transcriptional repressor for the JE gene.
 ...
PMID:Glucocorticoids inhibit the transcriptional induction of JE, a platelet-derived growth factor-inducible gene. 171 76

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)
 ...
PMID:Heparin-releasable platelet factor 4 in patients with coronary artery disease. 154 Oct 73

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

Fifty coronary male patients aged 34 to 63 (the mean age 46) and 32 normal male subjects aged 18 to 32 (mean age 23) were examined for the levels of Willebrand's factor, induced platelet aggregation, beta-thromboglobulin, thromboxane, prostacyclin levels, and vascular wall antiaggregation activity (by the cuff test). Basing on literature data and their own findings the authors come to a conclusion that elevated plasma concentration of Willebrand's factor combined with increased functional activity of platelets and reduced vascular wall antiaggregation activity is the key factor in the pathogenesis of atherosclerosis development and progress.
 ...
PMID:[Willebrand's factor, functional activity of blood platelets and antiaggregation activity of the vascular wall in ischemic heart disease]. 207 27

The influence of invasive investigations on parameters of hemostasis and fibrinolysis is generally unknown, although this has consequences for the design of prospective studies on the association between those parameters and regression or progression of atherosclerosis. We therefore determined hemostatic and fibrinolytic factors in 12 patients who were admitted to the hospital for coronary angiography (CAG; n = 5) or percutaneous transluminal coronary angioplasty (PTCA; n = 7). Blood samples were drawn under basal circumstances on the day before, the day of and the day after CAG or PTCA. Significant changes occur in the concentrations of platelets and white blood cells, hematocrit (Ht), von Willebrand factor antigen (vWF:ag), antithrombin III-activity (AT III-ag), antithrombin III-antigen (AT III-ant), fibrinogen, plasminogen, alpha2-antiplasmin (alpha2-AP), histidine-rich glycoprotein (HRG), and plasminogen activator inhibitor (PAI)-activity. Mean values of beta-thromboglobulin, platelet factor 4, factor VIII:C, tissue-type plasminogen activator activity (t-PA act) and euglobulin clot lysis time (ECLT) do not differ significantly. After correction for Ht, no significant differences exist between the day before and the day of the procedure; but on the day after CAG and PTCA significant differences occur in white blood cells, factor VIII:C, AT III-ag, alpha2-AP and PAI-act. It is concluded that principally blood samples for investigations on fibrinolysis may be taken on the day before or the day of CAG or PTCA without a loss of quality, if the values are corrected for Ht. Samples taken on the day after the procedure are not useful for such purposes.
 ...
PMID:The influence of coronary angiography and angioplasty on parameters of hemostasis and fibrinolysis. 214 44


1 2 3 4 5 6 Next >>