共查询到20条相似文献,搜索用时 15 毫秒
1.
Nanetti L Camilletti A Francucci CM Vignini A Raffaelli F Mazzanti L Boscaro M 《European journal of clinical investigation》2008,38(2):117-125
Background This study was performed to understand the metabolic effects of raloxifene, a selective oestrogen receptor modulator, on platelets in healthy non‐obese postmenopausal women. The data were compared to untreated subjects. Materials and methods Platelet nitric oxide activity (NO) and peroxynitrite level, platelet inducible and endothelial nitric oxide synthase expression and plasma lipids were evaluated at baseline and after 12 months of raloxifene or placebo treatment. Results A significant increase of platelet NO and reduction of platelet peroxynitrite levels, as well as a decrease of inducible nitric oxide synthase expression, was observed 12 months after raloxifene therapy as compared to baseline or placebo treatment. Moreover, raloxifene treatment caused a significant increase in high‐density lipoprotein cholesterol and a decrease of total cholesterol and low‐density lipoprotein cholesterol were observed versus baseline values (P < 0·05). A significant positive correlation was observed between high‐density lipoprotein cholesterol and platelet NO (r = 0·76, P < 0·005) in the raloxifene group. Conclusion Our results showed that raloxifene improves platelet metabolism in healthy postmenopausal women through an increase of the bioavailability of platelet NO by a reduction of iNOS and the beneficial effects on lipid metabolism. This mechanism of action of raloxifene on platelet activity may explain some cardiovascular protective effects of this selective oestrogen receptor modulator. 相似文献
2.
G. LUC H.-J. PARRA G. ZYLBERBERG J.-C. FRUCHART SERLIA INSERM 《European journal of clinical investigation》1991,21(1):118-122
Low levels of plasma high-density lipoprotein (HDL)-cholesterol and apolipoprotein (apo)-A-I are associated with premature coronary heart disease. However, particles in the density range of HDL are heterogeneous. Two main types of apo A-I-containing particles can be identified, one species containing both apo A-I and apo A-II (Lp A-I:A-II) and the other apo A-I but no apo-A-II (Lp A-I). This study was designed to measure HDL cholesterol, apo A-I, and, using a new procedure, Lp A-I in 233 healthy normolipidaemic young men (cholesterol less than 250 mg dl-1 and triglycerides less than 200 mg dl-1). Among these subjects, the composition of HDL was very variable as indicated by the 10th and the 90th percentiles of the HDL-cholesterol/apo A-I ratios which were 0.32 and 0.49, respectively. The 10th and 90th percentiles of apo A-I and Lp A-I:A-II were 126 and 167 mg dl-1 and 83 and 116 mg dl-1, respectively. On the other hand, Lp A-I showed a much larger variation, the 10th and 90th percentiles being at 33 and 62 mg dl-1, respectively. The distribution of individual values of Lp A-I showed that this fraction of apo A-I-containing particles was very variable among subjects, the Lp A-I/apo A-I ratio extending from 0.18 to 0.58. Triglycerides, Lp A-I and Lp A-I:A-II were correlated with HDL cholesterol, but no correlation between apo A-I containing subfractions and plasma triglycerides was noticed. Since preliminary results from angiographic and clinical studies show that Lp A-I could exert a protective role for atherosclerosis, it would seem that the measurement of Lp A-I might help in the future to characterize better the individual's risk for atherosclerosis. 相似文献
3.
Reverse cholesterol transport: relationship between free cholesterol uptake and HDL3 in normolipidaemic and hyperlipidaemic subjects 总被引:1,自引:0,他引:1
M. CASTRO CABEZAS G. P. H. VAN HEUSDEN† ‡ T. W. A. DE BRUIN J. R. C. M. VAN BECKHOVEN† L. A. W. KOCK K. W. A. WTRTZ† D. W. ERKELENS 《European journal of clinical investigation》1993,23(2):122-129
Abstract. High density lipoproteins (HDL) are responsible for the Reverse Cholesterol Transport (RCT). The role of the composition of the HDL particle in RCT, involving free cholesterol (chol) uptake from cell membranes, is not completely understood. We have therefore studied the uptake capacity from subjects with a wide variety of plasma HDL cholesterol concentrations in an HDL-receptor free model consisting of bovine heart mitochondrial membranes labeled with [14C]cholesterol. HDL were isolated by molecular sieve chromatography from fresh plasma samples of eight subjects with low plasma HDL chol concentrations (≤ 1.0 mmol L-1) and 15 subjects with normal HDL chol concentrations. The latter were subdivided into an intermediate (HDL chol: 1.0–1.4 mmol L-1; n= 9) and a high HDL chol group (>1.4 mmol L-1; n= 6). In the HDL fractions isolated by chromatography (cHDL), total chol and apolipopro-tein (apo) A1 were measured. Free chol uptake was significantly decreased by 32% in the tertile with the lowest plasma HDL chol (49 1 ± 15.8 arbitrary units; mean ± SD), compared to the tertile with high HDL chol (72.1 ± 16.6 au). Linear regression analysis showed a positive correlation between the free choi uptake and plasma HDL3 concentrations (r= 0.61; P<0.01), HDL chol (r= 0.56; P<0.01), HDL associated apo A1 (r = 0.46; P<0.05), cHDL apo AT (r = 0.56; P<0.05) and cHDL chol (r = 0.46; P<0.05) in all subjects combined. Stepwise multiple-regression analysis confirmed the association of [14C]cholesterol uptake with plasma HDL3 concentrations (β, 061; P= 0.004). No correlations were found between free chol uptake and total plasma apoAI (r = 0.26; ns) or HDL2 (r = 0.27; ns). After an oral fat load in four FCH patients, free chol uptake parallelled the changes in plasma HDL3 chol concentrations. We conclude that HDL3 is involved in the early steps of RCT and low HDL3 levels may result in less efficient RCT in hypertriglyceridemia. 相似文献
4.
PETRA LÖBEL ELISABETH STEINHAGEN-THIESSEN KARSTEN SCHRÖR 《European journal of clinical investigation》1988,18(3):256-260
Abstract. The effect of lowering total plasma and low density lipoprotein (LDL) cholesterol in heterozygous familial hypercholesterolaemia type IIa (FH) on platelet function, thromboxane (TX) formation and platelet sensitivity against iloprost, a stable prostacyclin mimetic, was studied in platelet-rich plasma ex vivo . Seven FH patients were treated with cholestyramine (12 g day-1 ) for 8–11 months and were compared with eight untreated FH patients and 11 healthy control subjects. In comparison with platelets from healthy controls, platelets from untreated FH patients exhibited a significantly increased aggregation response and TX formation, and a reduced reactivity against inhibition of platelet aggregation by prostacyclin. Treatment with cholestyramine for 8–11 months resulted in a 21% reduction in total serum and LDL-cholesterol. This was not accompanied by any change in platelet hyperreactivity or TX formation. However, cholestyramine treatment normalized the platelet reactivity of FH patients against iloprost, being no more different from healthy controls. It is concluded that reduction in plasma cholesterol by cholestyramine results in normalization of the reduced platelet sensitivity against prostacyclin. This might contribute to beneficial effects of cholestyramine treatment in preventing thrombembolic complications of atherosclerosis. 相似文献
5.
S J Shattil R Anaya-Galindo J Bennett R W Colman R A Cooper 《The Journal of clinical investigation》1975,55(3):636-643
Platelets from individuals with familial hypercholesterolemia show increased sensitivity to the aggregating atents, epinephrine and ADP. Since the mechanism of this abnormal sensitivity is unknown, we examined, in vitro, the influence of the plasma lipid environment on the function of platelets. The composition of plasma lipids was altered by the addition of sonicated cholesterol-dipalmitoyl lecithin liposomes which were "cholesterol normal" (cholesterol-phospholipid mole ratio [C/P] equals 1.0, "cholesterol rich" (C/P eauals 2.2), or "cholesterol poor" (C/P equals 0). Cholesterol-normal liposomes had no influence on platelet lipids or platelet function. In contrast, after incubation for 5 h at 37 degrees C with cholesterol-rich liposomes, normal platelets acquired 39.2% excess cholesterol with no change in phospholipids or protein. The percent increase in platelet membrane cholesterol was three-fold that of the granule fraction. The acquisition of cholesterol by platelets was associated with a 35-fold increase in sensitivity to epinephrine-induced aggregation (P less than 0.001) and 15-fold increase to ADP aggregation (P less than 0.001), as determined both by aggregometry and by [13C]serotonin release. Response to thrombin or collagen was unchanged. Platelets incubated with cholesterol-poor liposomes underwent a selective loss of 21.4% cholesterol and this was associated with an 18-fold reduction in their sensitivity to epinephrine. These studies demonstrate that the cholesterol content of platelets is dependent on the lipid composition of the milier. Cholesterol acquired by platelets may exert its effect on platelet function by a modification of the platelet membrane. 相似文献
6.
The Influence of Plasma Free Fatty Acids and Cholesterol on the Aggregation of Blood Platelets in Migraine Patients 总被引:1,自引:0,他引:1
SYNOPSIS
The Platelet Aggregate Ratio (PAR) was determined in 34 women with common migraine during headache-free intervals. Fourteen of them were studied also during migraine attacks.
The levels of FFA and total cholesterol in the blood were determined simultaneously to assess their influence on aggregation of blood platelets.
Plasma FFA levels rose significantly during headache (r<0.001). The levels of total blood cholesterol did not show a homogenous distribution. In 20 patients blood cholesterol was elevated; in the remaining 14 patients levels were within the standard range.
The migraineurs with high cholesterol showed a significantly lower PAR during headache-free intervals than did the control subjects (r<0.001). There was no significant difference between PAR in migraineurs with normal cholesterol and the controls. A significant fall of PAR during migraine attacks was observed only in migraineurs with high cholesterol (r<0.01). There was a significant correlation between the falling of PAR and the level of blood cholesterol (r<0.05). The same correlation was found between the falling of PAR and the rising of FFA during migraine attacks (r<0.05).
We suggest that FFA can raise the number of circulating platelet aggregates during migraine episodes. Total blood cholesterol is one of the factors which define migraine populations with respect to platelet aggregation. 相似文献
The Platelet Aggregate Ratio (PAR) was determined in 34 women with common migraine during headache-free intervals. Fourteen of them were studied also during migraine attacks.
The levels of FFA and total cholesterol in the blood were determined simultaneously to assess their influence on aggregation of blood platelets.
Plasma FFA levels rose significantly during headache (r<0.001). The levels of total blood cholesterol did not show a homogenous distribution. In 20 patients blood cholesterol was elevated; in the remaining 14 patients levels were within the standard range.
The migraineurs with high cholesterol showed a significantly lower PAR during headache-free intervals than did the control subjects (r<0.001). There was no significant difference between PAR in migraineurs with normal cholesterol and the controls. A significant fall of PAR during migraine attacks was observed only in migraineurs with high cholesterol (r<0.01). There was a significant correlation between the falling of PAR and the level of blood cholesterol (r<0.05). The same correlation was found between the falling of PAR and the rising of FFA during migraine attacks (r<0.05).
We suggest that FFA can raise the number of circulating platelet aggregates during migraine episodes. Total blood cholesterol is one of the factors which define migraine populations with respect to platelet aggregation. 相似文献
7.
白细胞对高胆固醇血症患者血小板聚集功能的影响 总被引:1,自引:0,他引:1
目的 :研究白细胞对高胆固醇血症患者血小板聚集功能的影响。方法 :对 72例高胆固醇血症患者与72例年龄相近的相同性别正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆LDL。测定LDL的电泳迁移率及硫代巴比妥酸反应物质含量。分别将这种脂蛋白加入由正常人新鲜富含血小板血浆构成的反应系统中 ,用血小板聚集仪分别测定ADP诱导的血小板 5分钟最大聚集率。结果 :HC患者血浆TC含量平均升高 1 6 7倍 ,LDLC平均升高 1 4 3倍 ,同时TBARS升高 1 2 2倍。HC组LDL的REM及TBARS含量均较对照组显著增加 (P <0 0 1) ,表明HC患者血浆LDL发生了氧化修饰生成Ox -LDL。PRP +WBC组较PRP组显著抑制血小板聚集 (P <0 0 1) ,降低 0 2 4倍 ,对照组LDL对血小板聚集无明显影响 ,HC组的LDL使MAR较对照组增高 (P <0 0 5 ) ,增加 0 0 7倍。WBC使HC组的MAR较空白、对照及未加WBC的HC组明显增加 (P <0 0 1) ,分别增加 0 14、 0 13和 0 0 8倍。结论 :白细胞使高胆固醇血症患者血小板聚集增加 相似文献
8.
OBJECTIVES: The circulating lipoproteins may cause some abnormalities in platelet composition and function in hypercholesterolemia. The aim of this study was to investigate whether platelet apoptosis, platelet activation, platelet aggregation, platelet-leukocyte aggregate (PLA) formation and lipid peroxidation occur simultaneously in hyperlipidemia. DESIGN AND METHODS: Expression of GpIIb/IIIa (CD41a), P-selectin (CD62-P), platelet-bound fibrinogen (antifibrinogen), platelet membrane phosphatidylserine (PS), platelet-monocyte aggregates (mono-PLA) and platelet-neutrophil aggregates (neut-PLA) was measured in eight hyperlipidemic and eight normal subjects using flow cytometry. ADP (10 microM) was used to activate platelets. Furthermore, ADP induced platelet aggregation responses, platelet malondialdehyde (MDA) and glutathione (GSH) levels were determined. RESULTS: Before platelet activation, platelet CD62-P, antifibrinogen, annexin-V, mono-PLA, neut-PLA and platelet MDA levels as well as platelet aggregation responses in the hyperlipidemics were significantly higher than those in the controls (P<0.01, P<0.01, P<0.01, P<0.001, P<0.001, P<0.01, P<0.001, respectively), whereas GpIIb/IIIa expression and GSH levels were not different significantly (P > 0.05). In the control group, CD62-P, antifibrinogen and annexin-V levels increased significantly after ADP activation (P<0.05, P<0.05, P<0.01, respectively). In hyperlipidemic subjects, annexin-V expression increased significantly after activation (P<0.01), whereas expression of GpIIb/IIIa, CD62-P and antifibrinogen remained unchanged (P>0.05). The levels of total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C), serum fibrinogen (S-FGN) and high density lipoprotein cholesterol (HDL-C) in patients were found to be correlated with platelet CD62-P, antifibrinogen, annexin-V, mono-PLA and MDA. CONCLUSIONS: In conclusion, it seems that in hyperlipidemia, some platelets are in an activated state in circulation, and that increased lipid peroxidation, early apoptosis, platelet-leukocytes aggregate formation and platelet aggregation altogether accompany this process. 相似文献
9.
The phospholipid composition and cholesterol content of platelet-derived microparticles: a comparison with platelet membrane fractions 总被引:1,自引:0,他引:1
É. BIRÓ J. W. N. AKKERMAN† F. J. HOEK G. GORTER† L. M. PRONK A. STURK R. NIEUWLAND 《Journal of thrombosis and haemostasis》2005,3(12):2754-2763
BACKGROUND: The processes that govern the distribution of molecules between platelets and the microparticles (MP) they release are unknown. Certain proteins are sorted selectively into MP, but lipid sorting has not been studied. OBJECTIVES: To compare the phospholipid composition and cholesterol content of platelet-derived MP obtained with various stimuli with that of isolated platelet membrane fractions. METHODS: Washed platelets from venous blood of healthy individuals (n = 6) were stimulated with collagen, thrombin, collagen plus thrombin, or A23187. Platelet activation, MP release and antigen exposure were assessed by flow cytometry. MPs were isolated by differential centrifugation. Platelet plasma-, granule- and intracellular membranes were isolated from platelet concentrates (n = 3; 10 donors each) by pressure homogenization and Percoll density gradient fractionation. The phospholipid composition and cholesterol content of MPs and membrane fractions were analyzed by high performance thin layer chromatography. RESULTS: The phospholipid composition of MPs was intermediate compared with that of platelet plasma- and granule membranes, and differed significantly from that of intracellular membranes. There were small but significant differences in phospholipid composition between the MPs produced by the various agonists, which paralleled differences in P-selectin exposure in case of the physiological agonists collagen, thrombin, or collagen plus thrombin. The cholesterol content of MPs tended to be higher than that of the three-platelet membrane fractions. CONCLUSIONS: Regarding its phospholipid content, the MP membrane is a composite of the platelet plasma- and granule membranes, showing subtle differences depending on the platelet agonist. The higher cholesterol content of MPs suggests their enrichment in lipid rafts. 相似文献
10.
S. Grgurevich R. Krishnan M. M. White L. K. Jennings 《Journal of thrombosis and haemostasis》2003,1(3):576-586
Summary. We investigated the direct role of cholesterol lowering on human platelet aggregation by in vitro cholesterol depletion using methyl-β-cyclodextrin. Collagen and thrombin receptor agonist peptide induced maximal aggregation was significantly decreased in cholesterol depleted platelets. In contrast, anti-CD9 antibody, mAb7, or anti-β3 antibody, D3, induced percent maximal aggregation was unaffected by cholesterol depletion. Surface and total αIIb β3 levels were equivalent in both groups. Morphological and ultrastructural analysis of collagen induced aggregates revealed that normal and cholesterol depleted platelets changed shape and aggregated; however, cholesterol depletion impaired microtubule ring formation and aggregate size. Cholesterol depletion also diminished the extent of the open canalicular system and collagen induced platelet ATP release. These data suggest cholesterol depletion impairs platelet aggregation by altering platelet ultrastructure critical in mediating secretion. Temporal differences and differences in tyrosine phosphoprotein levels following collagen stimulation were observed, thereby indicating that platelet signaling was concurrently affected by cholesterol depletion. 相似文献
11.
Platelet-modified low density lipoprotein induces macrophage cholesterol accumulation and platelet activation 总被引:1,自引:0,他引:1
M Aviram B Fuhrman S Keidar I Maor M Rosenblat G Dankner G Brook 《Zeitschrift für klinische Chemie und klinische Biochemie》1989,27(1):3-12
Low density lipoprotein (LDL), modified by chemical or biological means, was shown to induce macrophage cholesterol accumulation. The cholesterol and protein contents of LDL were decreased (by 10 and 15%, respectively) by incubation of the LDL for 2 h at 37 degrees C with normal washed platelet suspension or with platelet-conditioned medium; these decreases were not affected by platelet activation. The platelet-modified LDL caused a greater increase (by up to 15%) in collagen-induced, in vitro platelet aggregation than control LDL. Incubation of mouse peritoneal macrophages with platelet-modified LDL for 18 h at 37 degrees C resulted in an elevation of the macrophage cholesterol ester content (by 35-50%) as well as an increase in the cholesterol esterification rate (by 40-70%), compared with the effect of control LDL. Macrophage cholesterol synthesis, however, was significantly decreased (by 40-50%), compared with the effect of control LDL. The effect of LDL treated by platelet-conditioned medium was similar to that of platelet-modified LDL. The effect of platelet-modified LDL on macrophage cholesterol esterification was maximal within 24 h of incubation, and it was not significantly affected by inhibition of cholesterol synthesis. The platelet-modified LDL was taken up by the macrophages in a saturable fashion and its uptake was competitively inhibited by LDL, but not by acetylated LDL. We conclude that platelet-modified LDL interacts with the LDL receptor and induces macrophage cholesterol accumulation. Since the modified lipoprotein induces in vitro foam cell formation and platelet activation, platelet-modified LDL could be considered to be pro-atherogenic. 相似文献
12.
Seventeen patients with hypertriglyceridaemia were given a lipid-lowering diet with a high P/S-ratio 2.1 during a 3-week period. The very low density lipoprotein triglycerides decreased by 43%, low density lipoprotein cholesterol by 19% and high density lipoprotein cholesterol by 12%. There was a marked increase of linoleic acid (18:2 n-6) in all plasma lipid esters with a concomitant decrease of the saturated and monounsaturated fatty acids. There was a slight increase of the linoleic acid metabolites 18:3 n-6, 20:3 n-6 and 20:4 n-6 in serum triglycerides whereas the fatty acids of the n-3 series decreased in all plasma lipid esters. In the platelets a similar pattern was found with an increase of linoleic acid and its metabolite 22:4 n-6 and a decrease of 18:1 n-9 as well as of the n-3 fatty acids. No significant differences in platelet reactivity was found. However, in a few patients there was an increased platelet aggregation after the diet period. Our results suggest that this diet based on a very high content of linoleic acid may not affect platelet reactivity in a beneficial way. The reason may be an increased turnover of arachidonic acid in the platelets or an imbalance between the n-6 and n-3 series of fatty acids. 相似文献
13.
C Otto M Baumann T Schreiner G Bartsch H Borberg P Schwandt H Schmid-Sch?nbein 《European Journal of Ultrasound》2001,14(2-3):157-166
Most of the published studies concerning platelet aggregation were performed with chemical stimulation procedures, however, mechanical stimulation might be a better simulation of physiological activation of platelets. In order to evaluate the influence of ultrasound on platelet aggregation in vitro, we developed an ultrasound device in a standardized set-up, and we evaluated the influence of lipoproteins and the glycoprotein IIb/IIIa inhibitor tirofiban on ultrasound induced platelet aggregation. A cylindrical shaped plastic test tube with 1 ml of platelet-rich plasma was placed in an ultrasound bath (35 kHz) for 5 s. The ultrasound energy transfer into the sample (Delta W=3.77 J) was calculated using the average temperature increase (averaged by 0.935 degrees C) of the sample. Platelet aggregation was quantified immediately after stimulation with ultrasound or adenosine diphosphate (ADP 2.1 and 4.2 microM) by the Myrenne Aggregometer PA2 at low (40 s(-1)) and afterwards at high (2500 s(-1)) shear. To evaluate the influence of lipoproteins, seven healthy male volunteers were investigated before and after a fat load (50 g fat per m(2) body surface), and 11 patients suffering from hypercholesterolemia and atherosclerotic disease before and after a single low-density lipoprotein (LDL) apheresis. Platelet aggregation after ultrasound stimulation was well correlated with platelet aggregation after ADP (r between 0.50 and 0.95). However, when exposed to high shear, the low shear-induced platelet aggregates were more stable after ultrasound stimulation compared with ADP stimulation either with or without tirofiban. After the fat load triglyceride concentration increased from 0.86+/-0.39 to 2.10+/-1.10 mmol l(-1) (P<0.05) resulting in a reduced formation of platelet aggregates after weak (ADP 2.1 microM) but not after strong (ADP 4.2 microM or ultrasound) stimuli. After a single LDL apheresis LDL cholesterol dropped from 3.99+/-0.90 to 1.06+/-0.55 mmol l(-1) (P<0.005). No changes in platelet aggregation were observed with the exception of a lower aggregation when exposed to high shear after stimulation with 2.1 microM ADP. In conclusion, we found the ultrasound stimulation of platelet-rich plasma easy to perform. The platelet aggregation after ultrasound stimulation correlated well with stimulation after ADP. While a reduction in LDL cholesterol concentration had only slight effects on platelet aggregation, an increase in triglyceride concentration resulted in a reduced formation of platelet aggregates after weak stimulation. 相似文献
14.
T. M. QUINTON S. KIM† J. JIN† S. P. KUNAPULI† 《Journal of thrombosis and haemostasis》2005,3(5):1036-1041
ADP is important in propagating hemostasis upon its secretion from activated platelets in response to other agonists. Lipid rafts are microdomains within the plasma membrane that are rich in cholesterol and sphingolipids, and have been implicated in the stimulatory mechanisms of platelet agonists. We sought to determine the importance of lipid rafts in ADP-mediated platelet activation via the G protein-coupled P2Y1 and P2Y12 receptors using lipid raft disruption by cholesterol depletion with methyl-beta-cyclodextrin. Stimulation of cholesterol-depleted platelets with ADP resulted in a reduction in the extent of aggregation but no difference in the extent of shape change or intracellular calcium release. Furthermore, repletion of cholesterol to previously depleted membranes restored ADP-mediated platelet aggregation. In addition, P2Y12-mediated inhibition of cAMP formation was significantly decreased upon cholesterol depletion from platelets. Stimulation of cholesterol-depleted platelets with agonists that depend upon Galpha(i) activation for full activation displayed significant loss of aggregation and secretion, but showed restoration when simultaneously stimulated with the Galpha(z)-coupled agonist epinephrine. Finally, Galpha(i) preferentially localizes to lipid rafts as determined by sucrose density centrifugation. We conclude that Galpha(i) signaling downstream of P2Y12 activation, but not Galpha(q) or Galpha(z) signaling downstream of P2Y1 or alpha2A activation, respectively, has a requirement for lipid rafts that is necessary for its function in ADP-mediated platelet activation. 相似文献
15.
1. Repeated plasma exchange was carried out on three young patients with severe familial hypercholesterolaemia. There was a 3 week interval between each exchange. After a single exchange, plasma cholesterol, apolipoprotein B and low density lipoprotein-cholesterol levels decreased markedly, but pre-exchange levels were not achieved within 2 weeks. High density lipoprotein-cholesterol and apolipoprotein A-I levels also fell but returned to the original concentration after only 5 days. 2. Platelet aggregation and [14C]serotonin release were increased in all three patients and dropped by 20% and 13% respectively after a single plasma exchange. Platelet function in vitro returned to pre-exchange levels with similar kinetics to that observed with the low density lipoprotein concentration. On removal of 100 g of plasma cholesterol, after repeated exchanges, low density lipoprotein concentration and platelet function were significantly decreased in comparison with values before initiation of plasma exchange. In addition there was a marked regression of xanthoma in all three patients. 3. Since this procedure is instrumental in achieving a negative cholesterol balance as well as inhibiting hypersensitive platelets, it may well result in a downgrading of the atherosclerotic risk. 相似文献
16.
1. Plasma and platelet free catecholamine concentrations were measured in 22 normal subjects and in 10 treated and 11 untreated patients with heterozygous familial hypercholesterolaemia. 2. Plasma noradrenaline concentrations were significantly higher in both treated and untreated hypercholesterolaemic patients than in normal subjects. Adrenaline concentrations did not differ. 3. Platelet noradrenaline levels were higher in untreated hypercholesterolaemic patients than in normal subjects. 4. Positive correlations between the plasma noradrenaline concentration and the platelet noradrenaline concentration were observed in both normal subjects and hypercholesterolaemic patients. 5. Combining the data for normal subjects and hypercholesterolaemic patients revealed that the plasma noradrenaline concentration correlated positively with the plasma cholesterol concentration. The platelet noradrenaline concentration was also found to correlate with the plasma cholesterol concentration. 6. Our results suggest that an increased plasma cholesterol concentration may be associated with increased sympathetic nervous system activity as indicated by elevated plasma and platelet noradrenaline levels. Increases in circulating catecholamines may contribute to the platelet hyperaggregability seen in familial hypercholesterolaemia. 相似文献
17.
为探讨糖尿病及其血管病变时白细胞自发性活化的变化,对30例糖尿病患者及23例正常人进行了白细胞自发活化率(SAR)、血浆胆固醇、纤维蛋白原浓度及血小板聚集功能的测定。结果显示糖尿病患者白细胞SAR(%)显著高于正常对照组(P<0.01);胆固醇、纤维蛋白原及血小板聚集率也较正常对照组增高。提示:白细胞自发性活化与糖尿病及其血管病变的发生发展有关;胆固醇、纤维蛋白原及血小板聚集与白细胞自发性活化有关。 相似文献
18.
H Vinazzer 《Wiener klinische Wochenschrift》1984,96(24):889-893
In 20 patients suffering from primary hyperlipoproteinaemia the action of sultosilic acid piperazine salt (A-585) was compared with bezafribrate. In a double-blind cross-over study parameters of the lipoprotein metabolism, as well as of fibrinolysis and of platelet function were examined. Both drugs significantly diminished total cholesterol, triglycerides, beta- and pre-beta cholesterol whilst alpha-cholesterol increased. Moreover, both drugs caused a significant shortening of the euglobulin lysis time and a diminution of platelet adhesiveness. In patients under oral anticoagulants the thrombotest levels were not influenced by A-585, but were depressed by bezafibrate. A slightly elevated gamma-GT normalized during bezafibrate therapy but was not influenced by A-585. 相似文献
19.
Concentration of rafts in platelet filopodia correlates with recruitment of c-Src and CD63 to these domains 总被引:2,自引:3,他引:2
H. F. G. Heijnen †§ M. Van Lier § S. Waaijenborg † Y. Ohno-Iwashita‡ A. A. Waheed‡ M. Inomata‡ G. Gorter W. Möbius† J. W. N. Akkerman § J. W. Slot†§ 《Journal of thrombosis and haemostasis》2003,1(6):1161-1173
Summary. The molecular mechanism that causes non-adhesive, discoid platelets to transform into sticky dendritic bodies that form blood clumps is a complex series of events. Recently it has become clear that lipid microdomains—also known as rafts—play a crucial role in this process. We have used a non-cytolytic derivative of perfringolysin-O, a cholesterol binding cytolysin, that binds selectively to cholesterol-rich membrane domains, combined with confocal- and immunoelectron microscopy to visualize cholesterol-raft dynamics during platelet adhesion. In resting platelets cholesterol was uniformly distributed on the cell surface and confined to distinct intracellular compartments (i.e. multivesicular bodies, dense granules, and the internal membranes of α-granules). Upon interaction with fibrinogen, cholesterol accumulated at the tips of filopodia and at the leading edge of spreading cells. Stimulation with thrombin receptor activating peptide (TRAP) resulted in a similar redistribution of cholesterol towards filopodia. The adhesion-dependent raft aggregation was accompanied by concentration of the tyrosine kinase c-Src and the tetraspanin CD63 in these domains, whereas glycoprotein Ib (GPIb) was not selectively targeted to the raft clusters. c-Src, the tetraspanin CD63, and GPIb were recovered in biochemically isolated low-density membrane fractions. Disruption of rafts by depleting membrane cholesterol had no effect on platelet shape change but inhibited platelet spreading on fibrinogen and TRAP-induced aggregation. Our results demonstrate that cholesterol rafts in platelets are dynamic entities in the membrane that co-cluster with the tyrosine kinase c-Src and the costimulatory molecule CD63 in specialized domains at the cell surface, thereby providing a possible mechanism in functioning as signaling centres. 相似文献
20.
O M Kalinkina N V Perova V P Zykova N A Gratsianski? O E Mel'kina M A Sokolova R G Oganov 《Terapevticheski? arkhiv》1990,62(9):77-83
The diet enriched with omega-3 polyunsaturated fatty acids (5 g/day for 4 weeks) was applied to the treatment of patients (n-22) with angina pectoris occurring for the first time. Meanwhile 6 patients received the control diet similar to the fish one as regards the protein, fat, carbohydrate, cholesterol and caloric ratio. The control group patients showed no alterations in blood lipids and apoproteins of in platelet function. The patients who received the fish diet manifested an appreciable decrease in the concentration of triglycerides (p less than 0.01), a slight reduction of cholesterol content. The level of high density cholesterol remained unchanged. There was a decrease in the concentration of thromboxane (p less than 0.05) and in the platelet count (p less than 0.05). In some patients, individual reactions of ADP-induced platelet aggregation were revealed: from the lowering (-60-10%) seen in the third of the examined up to the rise (+10+90%) in the other third. The decrease of apoprotein A1 established as safe for the protective cholesterol-transport properties of high-density lipoproteins was established. 相似文献