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 level of beta-thromboglobulin (beta TG), a useful marker of in vivo platelet "release reaction,"was determined by radioimmunoassay in 69 patients, with three types of primary hyperlipidemia (IIa, IIb, IV) and compared with the findings in age- and sex-matched healthy controls and 57 patients with established atherosclerosis and peripheral vascular disease. Malondialdehyde (MDA) formation, used for assessment of prostaglandin synthesis, was determined in 51 and plasma platelet factor 4 (PF4), measured by radioimmunoassay, in 48 of the patients with hyperlipidemia. Results were correlated to five serum lipids and lipoprotein levels in the patients with hyperlipidemia. beta TG was significantly increased in the patients with hyperlipidemia and peripheral vascular disease, compared to those in the controls (p < 0.001); it was significantly higher in the patients with hyperlipidemia than in those with peripheral vascular disease. PF4 and MDA formation were also increased in the patients with hyperlipidemia, and significantly higher levels of MDA were obtained in patients with type IIb and type IV hyperlipidemia than in those with type IIa hyperlipidemia (p < 0.02). beta TG and MDA correlated weakly with total serum cholesterol triglycerides and very low density lipoprotein-triglyceride. There was also a significant correlation between beta TG and PF4, and MDA production. These results indicate that in vivo platelet "release reaction" and MDA formation are increased in hyperlipidemic patients. The release reaction is more enhanced in those with hyperlipidemia than in the patients with peripheral vascular disease. They suggest that the abnormal platelet function is related to the elevated levels of serum lipids and lipoproteins in the hyperlipidemic patients and not only to the atherosclerotic changes associated with hyperlipidemia.
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PMID:Enhanced in vivo platelet release reaction and malondialdehyde formation in patients with hyperlipidemia. 645 May 32

Some patients with clinical evidence of atherosclerosis and others with diabetes were compared with appropriate controls. The intraplatelet level of platelet factor 4 (PF4) was significantly decreased in the arteriopaths and was lower in the diabetics when compared with controls. Patients with transient ischaemic attacks and stroke have even lower values. Intravenous heparin liberates large amounts of PF4 from an unknown reservoir, perhaps the endothelium, into the plasma. Arteriopaths liberated significantly more PF4 than the controls and the diabetics most. If a second heparin injection is given 24 hr after the first, the resultant plasma PF4 level was on average half that achieved after the first injection and again the patients had higher levels than the controls. Thus the reservoir originally "emptied" of PF4 by the heparin had been partially refilled in 24 hr and the reservoir in the atherosclerotic patients then contained more than the controls. Patients with atherosclerosis and especially diabetics differ from controls in the PF4 content of their platelets and in their response to heparin and in the rate of refill of the "heparin-mobilisable pool of PF4".
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PMID:Intra-platelet platelet factor 4 (IP.PF4) and the heparin-mobilisable pool of PF4 in health and atherosclerosis. 649 55

Because platelet activation may be important in the worsening of coronary atherosclerosis, we used a radioimmunoassay for platelet factor 4 to study platelet behavior in patients with coronary-artery disease. Forty patients had paired blood samples withdrawn for measurement of the plasma level of platelet factor 4 before and after a standardized exercise-tolerance test. Twenty patients had positive tests, and 19 of those 20 had clinical or angiographic evidence of coronary-artery disease. Eleven of the 20 had a greater than 50 per cent increase in platelet factor 4 after exercise. The remaining nine had positive exercise tests without rises in platelet factor 4. Elevated levels returned to normal within 15 minutes of exercise. Eighteen of 20 patients with negative exercise tests had no rise in platelet factor 4 after exercise. We conclude that a subset of patients with coronary-artery disease and exercise-induced myocardial ischemia had evidence of platelet activation and secretion. (N Engl J Med 302:193-197, 1980).
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PMID:Platelet activation during exercise-induced myocardial ischemia. 735 Apr 60

We studied 27 non-insulin-dependent diabetics without apparent atherosclerosis (AS) to investigate whether abnormal platelet function is related to asymptomatic atherosclerosis in diabetes mellitus. The degree of AS was quantitatively evaluated by determining the intimal plus medial thickness (IMT) of the carotid artery wall with ultrasound high-resolution B-mode imaging. Based on our previous finding that the upper threshold of the IMT was 1.1 mm in healthy subjects, the patients were divided into the AS-positive group with the IMT > 1.1 mm, (n = 17) and the AS-negative group with the IMT < 1.1 mm (n = 10). Among five variables measured as the factors concerned with thrombogenesis, only plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were significantly higher in the AS-positive group than in the AS-negative group. Chronic administration of pentoxifylline (300 mg/day) significantly reduced the abnormally high plasma levels of beta-TG and PF4 in 7 patients of the AS-positive group to normal levels, without lowering the normal plasma beta-TG and PF4 levels in the remaining 10 patients. Pentoxifylline treatment did not affect the plasma levels of the 3 other variables, von Willebrand factor, 6-keto prostaglandin F1 alpha and thromboxane B2. This study suggests that the progress of atherosclerosis in diabetes mellitus is associated with in vivo platelet activation and platelet activation does not occur in diabetics without carotid atherosclerosis. Pentoxifylline may impede the vicious cycle in which atherosclerosis is accelerated by platelet activation.
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PMID:Platelet activation in diabetic patients with asymptomatic atherosclerosis. 795 14

Sixteen patients with lower limb atherosclerosis (LLAS) stage II-III received autotransfusions of blood irradiated by ultraviolet light. Vascular wall antithrombogenic properties assessed before the treatment in the patients and controls were found deteriorated in LLAS subjects. The cuff test did not affect the antithrombogenic characteristics. The course of autotransfusions produced a clinical improvement and strengthening of the antithrombogenic properties. The cuff test demonstrated a significant decline in platelet aggregation in response to ADP, thrombin, collagen, ristomycin, arachidonic acid; of platelet factor 4, thromboxane B2, beta-thromboglobulin. Concentrations of antithrombin III, plasminogen, prostacyclin rose. The autotransfusions were made on "Izolda" device MD-73 (1 ml of blood per 1 kg b. mass). Irradiation dose 750 J/m2, wave length 254 nm. Platelet aggregation was studied according to Born technique in O'Brien modification. Thromboxane B2, 6-keto-PGF1 alpha, beta-thromboglobulin and TF 4 were measured by radioimmunoassay, antithrombin III and plasminogen by chromogenic substrates.
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PMID:[The antithrombogenic properties of the vascular wall and platelet aggregation in patients with atherosclerosis of the arteries of the lower extremities following a course of treatment with UV-irradiated autologous blood transfusion]. 802 Jul 15

Platelet catecholamine content may reflect integrated plasma catecholamine concentrations over time. The present study aimed at examining sympathetic nervous system (SNS) involvement in essential hypertension by assessing platelet noradrenaline (NA) and typically beta-adrenoreceptor mediated responses to adrenaline (A) infusion as indices of sympathetic tone. Healthy white men were recruited by public advertising and screening (mean +/- SD): Hypertensives (n = 13, sitting blood pressure [BP] 153 +/- 13/106 +/- 7 mmHg, age 34 +/- 5 years, weight 83 +/- 10 kg) were compared to normotensives (n = 13, sitting BP 114 +/- 9/75 +/- 9 mmHg, age 30 +/- 6 years [n.s.], weight 82 +/- 9 kg [n.s.]). Loss of platelet granular contents (including NA) prior to analysis was minimized by studying young subjects (age range 20-40 years, minimal atherosclerosis), using arterial blood sampling, and processing blood immediately. These procedures resulted in plasma beta-thromboglobulin and platelet factor 4 levels which were not significantly different between groups. Sympathetic activation resulting from stress was minimized by not labelling subjects as either hypertensive or normotensive. Mean arterial platelet NA content was significantly higher in hypertensives (64 +/- 31 pg/mg of platelet weight) compared to normotensives (43 +/- 20 pg/mg, p < 0.05) both at baseline and following 35% expansion of the circulating platelet pool by A infusion (p < 0.05) and correlated with arterial NA in the hypertensives (r = 0.79, p < 0.002) but not in the normotensives (r = 0.04, n.s.). Similar increases in platelet and plasma A during infusion in both groups suggest unchanged platelet uptake capacity and plasma clearance in the hypertensive group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sympathetic nervous system involvement in essential hypertension: increased platelet noradrenaline coincides with decreased beta-adrenoreceptor responsiveness. 806 4

The platelet-aggregatory response, platelet-release factors and markers of thrombin generation in vivo were studied prospectively in 53 patients participating in a randomized clinical trial evaluating the influence of nicardipine on the progression of coronary atherosclerosis. Coronary lesions were measured quantitatively and progression was defined as a decrease in minimum diameter by > or = 0.4 mm. At repeat angiography 24 months after study entry, 20 of the 53 patients had progression of 28 coronary narrowings. Only thrombin-induced enhanced platelet aggregation differentiated patients with from those without coronary disease progression, with an estimated odds ratio of 2.49 (95% confidence interval 1.10 to 5.66). The aggregatory response to adenosine diphosphate, collagen, epinephrine and platelet-activating factor were not different in the 2 groups of patients, nor were measurements of platelet factor 4, beta-thromboglobulin, thromboxane B2, 6-keto-prostaglandin F1 alpha and fibrinopeptide A. During 46.8 months of follow-up after repeat angiography, coronary events occurred in 11 of the 20 with and 6 of the 33 without progression (difference 37%, p = 0.013, confidence interval 11 to 63%). Those with coronary disease progression and an enhanced thrombin-induced platelet aggregation had a worse prognosis than those with no disease progression and a low thrombin-induced platelet aggregation. Thus, patients with coronary disease progression and future coronary events have an enhanced thrombin-induced platelet aggregation. This platelet abnormality may be a marker of increased risk and may play a causative role in the development of coronary events.
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PMID:Platelet aggregation, coronary artery disease progression and future coronary events. 810 46

To date, selective extracorporeal low-density lipoprotein (LDL) removal can only be performed from plasma; that is, a plasma-cell separation step using a centrifuge or a plasma membrane separator is necessary initially. This article characterizes a new polyacrylate-based LDL adsorber directly applicable to whole blood. In vitro single-pass hemoperfusion tests using pooled donor blood showed quantitative adsorption of atherogenic LDL-cholesterol (LDL-C) and complete recovery of protective high-density lipoprotein C. Fibrinogen, another independent risk factor of atherosclerosis, was also adsorbed to a lesser extent. Single-pass ex vivo biocompatibility using fresh donor blood on-line was excellent and resulted in minimal cell loss. Neither signs of hemolysis nor activation of monocytes (interleukin-1 production) were detected. Only slight activation of leukocytes (elastase release) and thrombocytes (platelet factor 4 secretion) as well as of coagulation (thrombin-antithrombin complex formation) and complement (C3a, C5a generation) was observed. Under the experimental conditions used, the optimal anticoagulation regimen was 0.5 IU heparin plus 0.375 mg citrate/ml blood. Priming the column with a buffer of pH 7.4 containing heparin, citrate, and Ca2+ is recommended. In conclusion, this new adsorber exhibited selective LDL-C adsorption in vitro combined with excellent ex vivo biocompatibility and thus holds great promise for a successful clinical application in a closed-loop system in patients.
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PMID:Lipid apheresis by hemoperfusion: in vitro efficacy and ex vivo biocompatibility of a new low-density lipoprotein adsorber compatible with human whole blood. 833 41

Recent advances on platelet functions involved in atherosclerosis and subsequent thromboembolic diseases are reviewed. Platelets show multiple roles in hemostasis/thrombosis, wound healing, allergy, inflammation, metastasis of malignant cells and vasospasms through aggregation/secretion reaction. In atheromatous plaque, migration and proliferation of vascular smooth muscle cells and macrophages are the most prominent findings. In this pathological state, platelet may play as an enhancer by the secretion of bioactive substances including platelet-derived growth factor, serotonin and platelet factor 4. Investigation on platelet dynamics must be carried out not only for monitoring but also for the assessment of progressive factors in atherosclerotic disease.
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PMID:[Platelet functions in atherosclerosis]. 841 62

Platelets contain a vast number of biologically active molecules within cytoplasmic granules which are classified according to their respective distinct ultrastructures, densities and content. The alpha-granule is a unique secretory organelle in that it exhibits further compartmentalization and acquires its protein content via two distinct mechanisms: (1) biosynthesis predominantly at the megakaryocyte (MK) level (with some vestigial platelet synthesis) (e.g. platelet factor 4) and (2) endocytosis and pinocytosis at both the MK and circulating platelet levels (e.g. fibrinogen (Fg) and IgG). The currently known list of alpha-granular proteins continues to enlarge and includes many adhesive proteins (e.g. Fg, von Willebrand factor (vWf) and thrombospodin (TSP)), plasma proteins (e.g. IgG and albumin), cellular mitogens (e.g. platelet derived growth factor and TGF beta), coagulation factors (e.g. factor V) and protease inhibitors (e.g. alpha 2-macroglobulin and alpha 2-antiplasmin). More recently the inner lining of the alpha-granule unit membrane has been demonstrated to contain a number of physiologically important receptors including glycoprotein IIb/IIIa (alpha IIb beta 3) and P-selectin. The alpha-granules originate from small precursor granules which can be observed budding from the trans-Golgi network within the platelet precursor cell the MK. During MK maturation the alpha-granules become very prominent and are ultimately packaged into platelets during thrombopoiesis. The alpha-granular contents are destined for release during platelet activation at sites of vessel wall injury and thus play an important role in haemostasis, inflammation, ultimate wound repair and in the pathogenesis of atherosclerosis.
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PMID:Platelet alpha-granules. 846 33


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