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)

Plasma from 14 patients with severe and diffuse coronary atherosclerosis has been compared with that obtained from a normal control group. While a decreased heparin-thrombin clotting time was demonstrated in the patient group, suggesting an increased level of circulating platelet factor 4, there was no significant alteration in plasma antithrombin III level. These results do not support a recent suggestion of a mild chronic intravascular coagulation in atherosclerosis.
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PMID:Heparin neutralizing activity (HNA) and antithrombin III in coronary artery disease. 57 15

Since endothelial damage precedes sterol accumulation, platelet factor 4-like activity elevations and alterations in thrombocyte adhesiveness, it clearly is one of the earliest events in the pathogenesis of spontaneous pigeon atherosclerosis. Although the relationships among endothelial damage and the other events have not been elucidated, it is conceivable that products released from thrombocytes subsequent to adhesion on damaged endothelium may trigger other localized changes in the intimal cushion area and lead to the progression of atherosclerosis.
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PMID:Spontaneous endothelial cell injury in the intimal cushions of atherosclerotic pigeons. 92 22

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.
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PMID:Association between high levels of growth factors in plasma and progression of coronary atherosclerosis. 145 23

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.
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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)
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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.
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PMID:Relationship of platelet specific proteins and other factors to atherosclerosis in various stages of hypertension. 183 85

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.
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PMID:The influence of coronary angiography and angioplasty on parameters of hemostasis and fibrinolysis. 214 44

Plasma beta-thromboglobulin (beta TG) and platelet factor 4 (PF4) were significantly higher in a group of 116 hypertensive men than in a normotensive group of 142 men. They increased with the stage of hypertension but the level did not correlate with the age of the subjects. Platelet aggregation was similar in the two groups and positively correlated with the age of the subjects in the normotensive group but not in the hypertensive group. A strong positive correlation was observed between the levels of plasma beta TG and PF4 and between platelet aggregation to ADP and that to epinephrine in both the hypertensive and normotensive groups. However, there was no correlation between the level of plasma beta TG or PF4 and platelet aggregation. Plasma antithrombin III was lower in the hypertensive group than in the normotensive group. These studies suggest that plasma levels of beta TG and PF4 are closely related to the stage of hypertension and are better indicators than aggregation of in vivo platelet activation in hypertensive subjects. Enhanced platelet activation may be involved in the acceleration of hypertensive arteriovascular damage and atherosclerosis.
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PMID:Plasma concentrations of platelet-specific proteins in different stages of essential hypertension: interactions between platelet aggregation, blood lipids and age. 241 54

Forty-nine regions in 21 proteins were identified as potential heparin-binding sites based on the sequence organizations of their basic and nonbasic residues. Twelve known heparin-binding sequences in vitronectin, apolipoproteins E and B-100, and platelet factor 4 were used to formulate two search strings for identifying potential heparin-binding regions in other proteins. Consensus sequences for glycosaminoglycan recognition were determined as [-X-B-B-X-B-X-] and [-X-B-B-B-X-X-B-X-] where B is the probability of a basic residue and X is a hydropathic residue. Predictions were then made as to the heparin-binding domains in endothelial cell growth factor, purpurin, and antithrombin-III. Many of the natural sequences conforming to these consensus motifs show prominent amphipathic periodicities having both alpha-helical and beta-strand conformations as determined by predictive algorithms and circular dichroism studies. The heparin-binding domain of vitronectin was modeled and formed a hydrophilic pocket that wrapped around and folded over a heparin octasaccharide, yielding a complementary structure. We suggest that these consensus sequence elements form potential nucleation sites for the recognition of polyanions in proteins and may provide a useful guide in identifying heparin-binding regions in other proteins. The possible relevance of protein-glycosaminoglycans interactions in atherosclerosis is discussed.
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PMID:Molecular modeling of protein-glycosaminoglycan interactions. 246 27

We followed 19 men and 19 women with asymptomatic carotid stenosis up to 30 months to determine whether hematologic or lipid abnormalities could identify those individuals developing progressing carotid atherosclerosis (defined as an increase in mean percent stenosis greater than or equal to 19% or an increase in a single region of greater than or equal to 23%) on B-mode carotid ultrasonography performed at 2- to 6-month intervals. Our patients demonstrated increased beta-thromboglobulin, platelet factor 4, and fibrinogen compared with age-matched controls. Eight patients developed progression of carotid stenosis, and this group had higher baseline low-density lipoprotein (LDL) and fibrinogen than the 30 nonprogressing patients. Multiple regression analyses of age, sex, smoking, coronary artery disease, peripheral vascular disease, diabetes, hypertension, and baseline high-density lipoprotein (HDL), HDL2, HDL3, LDL, beta-thromboglobulin, platelet factor 4, and fibrinogen identified coronary artery disease and elevated LDL and fibrinogen as the only independent variables significantly associated with the progressing group. We conclude that, in patients with carotid atherosclerosis, a combination of coronary artery disease and elevated LDL and fibrinogen will predict with 88% accuracy whether the patient will have progressing carotid stenosis.
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PMID:Prediction of carotid stenosis progression by lipid and hematologic measurements. 218 78


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