Update on lipids, inflammation and atherothrombosis

Atherosclerosis is an inflammatory disease that involves the arterial wall and is characterised by the progressive accumulation of lipids in the vessel wall. The first step is the internalisation of lipids (LDL) in the intima with endothelial activation which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. These events increase LDL particles accumulation in the extracellular matrix where they aggregate/fuse, are retained by proteoglycans and become targets for oxidative and enzymatic modifications. In turn, retained pro-atherogenic LDLs enhance selective leukocyte recruitment and attachment to the endothelial layer inducing their transmigration across the endothelium into the intima. While smooth muscle cell numbers decline with the severity of plaque progression, monocytes differentiate into macrophages, a process associated with the upregulation of pattern recognition receptors including scavenger receptors and Toll-like receptors leading to foam cell formation. Foam cells release growth factors, cytokines, metalloproteinases and reactive oxygen species all of which perpetuate and amplify the vascular remodelling process. In addition, macrophages release tissue factor that, upon plaque rupture, contributes to thrombus formation. Smooth muscle cells exposed in eroded lesions are also able to internalise LDL through LRP-1 receptors acquiring a pro-thrombotic phenotype and releasing tissue factor. Platelets recognise ligands in the ruptured or eroded atherosclerotic plaque, initiate platelet activation and aggregation leading to thrombosis and to the clinical manifestation of the atherothrombotic disease. Additionally, platelets contribute to the local inflammatory response and may also participate in progenitor cell recruitment.     

Influence of lipids metabolism on platelet activation in vivo

Platelet aggregability and plasma factor VIII-related antigen (F. VIIIR:AG) level in 16 ischemic heart disease (IHD) patients were increased by isometric exercise and these changes were prevented by administration of a lipid lowering agent, simfibrate, a derivative of clofibrate. Serum total cholesterol (TC) level decreased and the high density lipoprotein-cholesterol (HDL-C)/TC ratio increased with the treatment. Another 7 hyperlipidemics were administered with simfibrate. Platelet malondialdehyde (MDA) production decreased with improvement in lipid profile. In an in vitro study, platelet aggregability and the plasma level of von Willebrand factor (vWF) and F.VIIIR:AG of normal citrated blood were increased by passing it through a glass bead column. Combining above results of the three separate studies, it would be suggested that hyperlipidemia might enhance platelet activation in vivo, which occurred through contact of platelets to atherosclerotic rough vessel surface. The anti-platelet effect of simfibrate might be mediated through its effect on arachidonic pathway in platelets.     

Serum lipids in stroke

In 60 patients with brain strokes the changes in serum triglycerides, cholesterol and optic density were determined in various stages of brain stroke. The control group included 60 patients without clinical evidence of atherosclerosis. Changes were observed in serum lipids in patients during brain stroke and they concerned mainly the levels of cholesterol and triglycerides. The intensity of these changes reflected the severity of the condition of the patient. In all patients the serum cholesterol level decreased during the first 7 days of the disease. In the group with favourable outcome a rise was observed in the cholesterol level after 4 weeks of disease. In the group with unfavorable course of the disease the level of cholesterol continued to fall until death. The triglyceride level was significantly lower in all patients in the 1st week of the disease in relation to the control group. After 4 weeks of the disease the triglyceride level rose to values not significantly different from those in the control group. The value of optic density of the serum in the group of patients in different stages of the disease was not statistically different from that in the control group. Determinations of serum lipids in patients with brain strokes together with clinical evaluation of the state of the patient seem to be useful in establishing prognosis in the disease.     

Effects of gemfibrozil on lipids and haemostasis after myocardial infarction

The effects of gemfibrozil on haemostatic variables were studied in 43 survivors of myocardial infarction with serum triglycerides (TG) greater than or equal to 2 mmol/l 2 weeks prior to randomization. The study was double-blind, placebo-controlled and stratified for chronic betablockade. Twenty-two individuals were given gemfibrozil 600 mg twice daily and 21 individuals received matching placebo. After 8 weeks the TG level was unchanged in the placebo group, whereas a 44% reduction was noted in the gemfibrozil group (p less than 0.001). Fibrinogen increased in both groups, while bleeding time and platelet count were unchanged. Clotting factor VII-phospholipid complex decreased in both groups, but the change was more marked and attained statistical significance only in the gemfibrozil group (60% reduction, p less than 0.01). By DDAVP-stimulated D-Dimer agglutination test 8 in 21 patients in the placebo group (38%) still had reduced fibronolytic capacity versus none in the gemfibrozil group (p = 0.001). Thus, in this study, gemfibrozil improved reduced fibrinolytic capacity and may have reduced hypercoagulability by lowering the clotting factor VII-phospholipid complex.     

Effect of exogenous lipids on rat brain cholesterol ester hydrolases

The three cholesterol ester hydrolases in rat brain were activated by varying degrees when a mixture of whole brain lipids was added to the respective assay systems. The lipid mixture could not replace the detergents present in the standard assay systems for the myelin-localized (pH 7.2) and the microsomal (pH 6.0) cholesterol ester hydrolases. However, the lipid mixture not only could replace the detergent in the pH 4.2 hydrolase assay system but also markedly activated the enzyme when the detergent was omitted. Exogenous phosphatidylserine, G_M1-ganglioside, stearic acid, and oleic acid all showed distinct and widely varying effects on each of the measured activities of the three cholesterol ester hydrolases. While the mechanism of activation or inhibition of these enzymes by exogenous lipids is not clear at present, these observations suggest potential importance of various lipids in the in vivo metabolic regulation of brain cholesterol ester metabolism.     

Adverse effects of psychiatric drugs on glucose and lipids metabolism

Psychiatric drugs bring indeniable benefits for the treatment of psychiatric disorders. But their use can come along with a varying degree of side effects, some of them known for a long time, and some that are at present starting to focus attention. In this group we can find metabolic side effects, because of their possible relationship with the mortality of patients with severe psychiatric disorders. In this article, effects of psychiatric drugs on glucose and lipids metabolism are revised.     

Serum lipids and anticonvulsants

The serum lipid levels of 200 epileptics (aged 20 to 40 years) undergoing long-term treatment with anticonvulsants were measured and compared with the levels of a normal population of the same age. The epileptics had higher serum lipid levels (especially of apolipoprotein B and HDL-cholesterol) but no higher incidence of hyperlipemias. A correlation between LDL-cholesterol and vitamin E has been found in epileptics, but it was not as significant as in normals. In male epileptics, positive correlations between the average daily dose of anticonvulsants (especially of those with a well-known enzyme-inducing effect) and triglycerides, cholesterol and LDL-cholesterol were found; in females there were no significant correlations.     

The effect of intramuscular stanozolol on fibrinolysis and blood lipids

The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p < 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p < 0.01) and remained elevated for three weeks. HDL cholesterol fell (p < 0.01) and both total and LDL cholesterol increased (p < 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.     

Serum lipids after stroke

To ascertain the appropriate time for detecting lipid abnormalities for prophylaxis, serial analyses of fasting serum lipoproteins were undertaken prospectively in men with cerebral infarction or transient ischemic attacks. Serum total cholesterol (T CHOL) and low density lipoprotein cholesterol (LDL CHOL) in cerebral infarction patients aged 50 to 69 were lowest on day 7, intermediate on day 1, and highest at 3 months, whereas very low density lipoprotein and high density lipoprotein cholesterol (HDL CHOL) changed little. The day 1 mean fasting serum HDL CHOL of cerebral infarct patients was significantly lower in subjects aged 50 to 59 than in those aged 60 to 69 (23 +/- 3 versus 42 +/- 5 mg/dl), and there was a corresponding higher ratio of T CHOL:HDL CHOL (12.7 +/- 4.5 versus 4.7 +/- 0.4, p less than 0.01). Mean HDL CHOL levels were low normal to low in patients aged 50 to 69 with transient ischemic attacks. Both serum cholesterol and triglyceride levels are initially decreased in patients aged 50 to 69 with cerebral infarction, whereas only cholesterol is decreased in patients 60 to 69 with transient ischemic attacks. Important lipoprotein abnormalities may be missed in the acute phase.     

Bioactive lipids in schizophrenia

Bioactive lipids, in particular arachidonic acid (AA), are vital for monoaminergic neurotransmission, brain development and synaptic plasticity. Phospholipases A2 (PLA2) are key-enzymes in AA metabolism and are activated during monoaminergic neurotransmission. Reduced membrane AA levels, and an altered activity of PLA2 have been found in peripheral membranes of drug-na?ve patients with schizophrenia with some conflicting results in more chronic patient populations. Furthermore, in vivo brain phosphorus-31 magnetic resonance spectroscopy suggests reduced lipid membrane precursors (phosphomonoesters) and increased membrane breakdown products (phosphodiesters) in drug-na?ve or early treated first-episode schizophrenia patients compared to age-matched controls or chronic populations and these changes were correlated with peripheral red blood cell membrane AA levels. We postulate that processes modulating membrane lipid metabolism are associated with psychotic illnesses and might partially explain the mechanism of action of antipsychotic agents, as well as experimental agents such as purified ethyl-eicosapentaenoic acid (E-EPA). Recent supplementation trials suggest that E-EPA is a modestly effective augmentation treatment resulting in reduced doses of antipsychotic medication in acutely ill patients with schizophrenia (but not in residual-type schizophrenia). This review investigates the role of bioactive lipids in schizophrenia and its treatment, as well as its potential use in prevention.     

脑梗塞患者血小板膜流动性与血脂的相关研究

本文对４９例脑梗塞病人的血小板膜流动性，血脂及血浆载脂蛋白进行了测定，发现脑梗塞患者血小板膜流动性显著低于对照组，与血浆ＬＤＬ／ＨＤＬ、ＡｐｏＢ呈明显负相关，与ＡｐｏＡ－１呈正相关，而与血浆胆固醇无明显相关性，提示：检血浆脂质、载脂蛋白能够很好的反映血小板膜流动性的改变。     

The apparent effects of ziprasidone on plasma lipids and glucose.

BACKGROUND: We examined the effects of ziprasidone on body mass index (BMI) and serum levels of glucose, cholesterol, and triglycerides. METHOD: As part of a multicenter study examining different strategies for switching to ziprasidone from other antipsychotics, we evaluated weight and serum glucose, cholesterol, and triglyceride measurements at baseline and following 6 weeks on ziprasidone treatment in 37 patients at our site. RESULTS: Short-term treatment with ziprasidone appeared to lead to significant reduction in serum cholesterol (p < .001) and triglyceride levels (p = .018) independent of changes in BMI. Ziprasidone treatment appeared to have no significant effect on BMI or glucose level, perhaps due to the small number of subjects. CONCLUSION: Ziprasidone appears to independently lead to a lowering of serum lipid levels.     

缺血性脑血管病患者的血脂水平

目的分析缺血性脑血管病（ICVD）患者的血脂水平，为今后预防保健及康复干预决策的制定提供依据。方法在佛山市第一人民医院病案数据库中检索1991-2004年诊断为ICVD的病例共2886例，其中2000-2004年ICVD患者共1430例为一亚组，以我院同时期保健科随机选取的400名健康体检人群为对照组，记录血脂情况，进行对照分析。结果血TC、TG和LDL—C水平ICVD患者组明显高于健康体检人群，差异有统计学意义。男女两性血脂水平均随年龄增加而逐渐增高，50岁以上女性血脂水平明显高于同龄组男性。血脂代谢异常患病率随着年代的推移呈逐步上升趋势，总胆固醇从1991—1994年的24．5％到2001-2004年的38．1％（男性）和22．3％到38．5％（女性），且明显高于国内2000-2001年普查人群高脂血症的患病率。结论佛山地区血脂异常是ICVD的重要原因之一。     

高通量透析膜对C-反应蛋白及血脂代谢的影响

背景：传统低通量透析不能改善微炎症状态和脂质代谢紊乱,新型的高通量透析则可以很好的改善这种微炎症状态和脂质代谢,有助于提高患者的生活质量和存活率,因此如何改善微炎症状态和脂质代谢成为人们研究的热点。 目的：观察高通量和低通量聚砜膜血液透析器对维持性血液透析患者血浆超敏C-反应蛋白及血脂代谢的影响。 方法：将44例维持性血液透析患者随机分为高通量透析组和低通量透析组,另选22例健康体健者作为正常对照组。高通量透析组使用高通量透析器FX60,低通量透析组使用低通量透析器F6,均每周透析3次,每次透析4 h;治疗1年后,分别比较两组患者治疗前后及与正常对照组的血超敏C-反应蛋白与总胆固醇、三酰甘油及低密度脂蛋白胆固醇等指标的变化。 结果与结论：两组治疗前血浆超敏C-反应蛋白与三酰甘油、总胆固醇及低密度脂蛋白胆固醇水平均高于正常对照组(P < 0.05);治疗后高通量透析组患者的血浆超敏C-反应蛋白与总胆固醇、三酰甘油及低密度脂蛋白胆固醇水平明显下降(P < 0.05),而低通量透析组无明显变化(P > 0.05)。结果提示采用高通量FX60聚砜膜透析器进行透析能改善维持性透析患者的微炎症状态及脂质代谢。 关键词：高通量透析;血液透析膜;血浆超敏C-反应蛋白;血脂;膜材料 doi:10.3969/j.issn.1673-8225.2010.25.032