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)

We have shown that the isoelectric point of thrombin is high and that thrombin is a cation at the pH of blood. On the other hand, prothrombin has a low isoelectric point, being more anionic at the pH of blood. It was also found that thrombin adsorbs readily to surfaces, especially negatively charged surfaces, like behenic acid surfaces at pH 8.2. Furthermore, thrombin adsorbed onto behenic acid was active in the sense that it coagulated fibrinogen. The significance of the electric charge of the thrombin molecule in the mechanism of atherosclerosis is discussed.
 ...
PMID:The isoelectric point of thrombin and its behaviour compared to prothrombin at some solid surfaces. 4 37

The following clinical groups of volunteers were studied: patients long after recovery from myocardial infarction (MI), others after recovery from deep vein thrombosis (DVT), patients with intermittent claudication, with diabetes, and male and female controls who were well matched. All were subjected to many platelet and clotting tests together with clinical, biochemical and haematological measurements in an attempt to find long term abnormalities in these various diseases. The male MIs differed very significantly from the controls in having much more heparin neutralizing activity (P less than 0.001)and less anti-thrombin (P less than 0.01). Less significantly, some bleeding time tests indicated less bleeding and the patients' platelets were larger. The females with MI had in general the same abnormalities but to a lesser degree. The patients with intermittent claudication, none of whom had a history of MI, had almost the same abnormalities and to the same degree. In deep vein thrombosis the heparin neutralizing activity was also clearly increased; the other tests were generally in the same direction but many were not significant. The diabetics had shorter bleeding times but little else abnormal relative to the controls, suggesting a different pathological process. When all male patients and controls were "scored" according to the degree of atherosclerosis there was a close overall correlation between the degree of atherosclerosis and the increase in the HNA level (r = --0.50, n = 66, P less than 0.001) and the decreased anti-thrombin (r = 0.25, n = 66, P less than 0.05).
 ...
PMID:Blood changes in atherosclerosis and long after myocardial infarction and venous thrombosis. 5 92

A quantitative assay for fibrin or other insoluble fibrin-like antigens ("fibrin") in small samples of intima is described. Tissue samples were subjected to electrophoresis directly from the intima into an antibody-containing gel to remove and measure fibrinogen and other soluble fibrin reactive antigens (FRA). The residual tissue was then exhaustively incubated with plasmin, and the soluble fragments generated from the insoluble "fibrin" were measured by quantitative immunoelectrophoresis. "Fibrin" accounted for about 2% of the tissue dry weight in normal intima and the ratio fibrinogen/"fibrin" was 1-1.5. In the gelatinous lesions, which seem to be the precursors of fibrous plaques, there was a small increase in "fibrin" but a substantial increase in fibrinogen and low density (LD)-lipoprotein, and the ratio fibrinogen/"fibrin" rose to about 3, which suggests that the increase in "fibrin" is secondary to increased permeation of fibrinogen. At the edges of large plaques there was also a threefold increase in fibrinogen, but "fibrin" increased fivefold, and accounted for 10% of the tissue dry weight. The same high concentration was found in the centres of large fibrous plaques with advanced atheroma lipid. Raised levels of "fibrin" were accompanied by raised levels of fibrinogen in most tissue samples. About 80% of the total soluble FRA could be clotted with thrombin; there was no significant difference between normal intima and lesions, and the proportion clotted was not related to "fibrin" content.
Atherosclerosis
PMID:Insoluble "fibrin" in human aortic intima. Quantitative studies on the relationship between insoluble "fibrin", soluble fibrinogen and low density lipoprotein. 23 64

A recently described platelet coagulant activity (factor X activating activity), whose pathophysiological significance is as yet unknown, was studied in rats fed a fat-rich (thrombogenic) diet for 1, 2 and 7 weeks and compared to rats fed normal laboratory chow. Whatever the duration of the special feeding period, a highly significant shortening of the clotting time, used for measuring this activity, was observed. When the platelet coagulant activity of individual "fat-fed"rats was quantitated by reference to that of individual control animals, we found a mean increase of 350% (n = 9) after one week and 267% (n = 3) after two weeks of dietary treatment. Partial thromboplastin time, thrombin time and soluble fibrin monomer complexes did not differ in control and treated animals. It seems that platelet coagulant activity, as measured in our test system, is one of the first laboratory parameters to be modified by fat-rich diets. These findings may be relevant to an understanding of the role of platelet coagulant activities other than platelet factor 3 in thrombotic phenomena.
Atherosclerosis 1979 Jun
PMID:Early increase of a new platelet coagulant activity in rats fed a thrombogenic diet. 47 81

Results in animals and in man indicate that in many circumstances, lipemia is not closely related to the severity of atherosclerosis nor to the incidence of coronary heart disease (CHD) or the intake of saturated fats as observed in paired studies between farmers from Moselle and Var in France and from West and East Scotland. In rabbits, an increased response of platelets to thrombin occurs before any deposition of cholesterol, as a result of a saturated fat feeding. Under these conditions, the addition of alcohol to the drinking water decreases significantly both the platelet response to thrombin and the severity of atherosclerotic lesions without much affecting plasma cholesterol. In farmers from Moselle and Var (as well as from Scotland), platelet functions, namely the aggregation to thrombin and their clotting activity, i.e. PF3, are closely related to the intake of saturated fats, either as a result of the long-term feeding or of a 1 year change in the diet of Moselle farmers. Certain platelet functions appear to be the only blood parameter related to the incidence of CHD and significantly correlated on a group, as well as on an individual basis, with the intake of saturated fat, and inversely related with that of calcium. Saturated fats and calcium are known to be the two main dietary factors related to CHD. These results suggest that the intermediate link between dietary fats and CHD might be blood platelets rather than serum lipids, through an effect on both thrombosis and atherosclerosis.
 ...
PMID:Dietary fats and platelet functions in relation to atherosclerosis and coronary heart disease. 51 Oct 11

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.
 ...
PMID:Heparin neutralizing activity (HNA) and antithrombin III in coronary artery disease. 57 15

Twelve healthy male subjects were maintained on a saturated fat (SF) dietary regimen followed by a polyunsaturated fat (PUF) regimen. At selected intervals a number of tests were carried out to assess the effect of SF or PUF on platelet composition and activation. Concomitant with the fall in serum cholesterol, associated with the PUF diet, there was a decrease in plasma heparin neutralizing activity (as measured by the heparin--thrombin clotting time), and a fall in the number of circulating platelet aggregates was also observed. These two parameters suggest diminished platelet activation. Malondialdehyde production (an index of prostaglandin synthesis) was unchanged throughout the two dietary periods. Changes in the quality of the dietary fat were manifested in the phospholipid fraction of platelet lipids, particularly phosphatidyl choline and sphingomyelin. Platelet counts of whole blood were significantly decreased when subjects were consuming PUF, but not all of these alterations were reflected in platelet-rich plasma. These results indicate that platelets may be activated in apparently normal people consuming a SF diet (the standard diet of developed countries) and that this activation may be decreased by replacement of dietary SF with PUF.
Atherosclerosis 1978 Nov
PMID:Modification of human platelet function by a diet enriched in saturated or polyunsaturated fat. 71 38

The wall of lover-limb arteries affected with severe atherosclerosis contains a Complex of substances with pro- and anticoagulative activities. The arterial wall, traumatized in endarterectomy by separation of the individual coats, releases procoagulative substances into blood circulation. The most conspicuous local manifestations of hypercoagulation and hypofibrinolysis appear on the day of surgery. The artery operated upon releases the thromboplastic factor for nine days; substances shortening the thrombin time (antiheparin substance, thrombin accelerator), for five days; and inhibitors of fibrinolysis, for four days after operation. A correlation was found between the regenerative process in the endarterectomized artery and the dynamics of the release of tissue factors influencing the haemocoagulation.
 ...
PMID:Arterial-wall tissue factors influencing haemocoagulation, and their release into circulation in endarterectomy. 114 57

Effects of phenformin on blood sugar, serum triglyceride, thrombin time, euglobulin clot lysis time and cardiovascular complications were studied in maturity onset diabetes and in atherosclerotic patients with or without diabetes, for a period of 14-18 months. Phenformin has shown the characteristic properties of an antifibrinopathic agent in that it prolongs thrombin time and enhances fibrinolysis. The hypoglycaemic effect of phenformin was found to be directly related to its antifibrinopathic action. Plasma lipids fell in all cases. Absence of fresh cardiovascular complications and improvement in anginal symptoms were observed. The metabolic, haematological and clinical benefits of phenformin and its limitations in maturity onset diabetes and atherosclerosis may be explained by the effects of the drug upon the thrombin-fibrinogen reaction. These results lend support to the hypothesis of a primary fibrinopathic pathogenesis in maturity onset diabetes mellitus and atherosclerosis.
 ...
PMID:Antifibrin action of phenformin. 114 44

Experiments were designed to examine the effect of oxidized low density lipoproteins (Ox-LDLs) on the expression and the release of endothelin from cultured endothelial cells and intact blood vessels. Ox-LDLs (30-300 micrograms/ml), but not native low density lipoproteins (200 micrograms/ml), stimulated the expression of preproendothelin mRNA in porcine and human endothelial cells, leading to a time- and concentration-dependent release of the peptide into the culture medium. The Ox-LDL-stimulated release of endothelin was mimicked by acetylated low density lipoprotein and abolished by downregulation of protein kinase C by phorbol ester. In the intact porcine aorta, Ox-LDLs, but not native low density lipoproteins, also increased the release of peptide in an endothelium- and concentration-dependent manner. The maximal effect was observed at a concentration of 100 micrograms/ml. Incubation of the intact porcine aorta with the scavenger receptor antagonist dextran sulfate decreased the formation of endothelium evoked by Ox-LDLs. The Ox-LDL-stimulated production of the peptide was further augmented in the presence of thrombin (4 units/ml) and was unaffected by nitric oxide-generating compound 3-morpholinosydnonimine (10(-5) M). These results suggest that Ox-LDL may be an endogenous mediator of the augmented release of endothelin observed in hyperlipidemia and atherosclerosis. The increased production of the peptide could contribute to vasospastic events and may promote vascular smooth muscle proliferation and progression of atherosclerotic vascular disease.
 ...
PMID:Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. 131 34


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