Cyclic tensile stretch load and oxidized low density lipoprotein synergistically induce lectin-like oxidized ldl receptor-1 in cultured bovine chondrocytes, resulting in decreased cell viability and proteoglycan synthesis.

Mechanical stimulation is known to be an essential factor in the regulation of cartilage metabolism. We tested the hypothesis that expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) can be modulated by cyclic tensile stretch load in chondrocytes. Cyclic loading of repeated stretch stress at 10 cycles per minute with 10 kPa of stress for 6 h induced expression of LOX-1 to 2.6 times control in cultured bovine articular chondrocytes, equivalent to the addition of 10 microg/mL oxidized low density lipoprotein (ox-LDL) (2.4 times control). Application of the cyclic load to the chondrocytes along with 10 microg/mL ox-LDL resulted in synergistically increased LOX-1 expression to 6.3 times control. Individual application of cyclic loading and 10 microg/mL ox-LDL significantly suppressed chondrocytes viability (84.6% +/- 3.4% and 80.9% +/- 3.2% of control at 24 h, respectively; n = 3; p < 0.05) and proteoglycan synthesis [81.0% +/- 7.1% and 85.7% +/- 5.2% of control at 24 h, respectively; p < 0.05 when compared with 94.6% +/- 4.6% for native-LDL (n = 3)]. Cyclic loading and 10 microg/mL ox-LDL synergistically affected cell viability and proteoglycan synthesis, which were significantly suppressed to 45.6% +/- 4.9% and 48.7% +/- 6.7% of control at 24 h, respectively (n = 3; p < 0.01 when compared with individual application of cyclic loading or 10 microg/mL ox-LDL). In this study, we demonstrated synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis in chondrocytes, which may be mediated through enhanced expression of LOX-1 and which has important implications in the progression of cartilage degeneration in osteoarthritis.     

两种清除法测定低密度脂蛋白胆固醇的临床评价

目的对表面活性剂清除法 (SUR法 )和过氧化氢酶清除法 (CAT法 )两种低密度脂蛋白胆固醇 (LDL C)均相测定法进行临床评价。方法将上述两种方法与聚乙烯硫酸沉淀法 (PVS法 )进行比较 ,分析各自方法的精密度、准确性、特异性和干扰因素。结果两种清除法与PVS法 (X)具有良好的相关性 ,SUR法 (Y1) :Y1=0 .9311X +0 .10 2 2 ,r =0 .980 1;CAT法 (Y2 ) :Y2 =0 .94 0 1X +0 .0 991,r=0 .9832。高、中、低三种LDL C浓度混合血清所测定结果表明两种方法均具有良好的精密度 ,总CV值SUR法 3.4 5 - 3.89% ,CAT法 3.5 1- 3.99% ,均达到临床满意的程度。两法线性范围均较宽 (线性均至 8.2 2mmol/L) ,最低检测浓度均为 0 .12mmol/L ,平均回收率SUR法为 98.0 % ,CAT法为 97.6 %。TG <14 .2mmol/L ,Hb <5g/L ,HDL C <3.88mmol/L ,胆红素 <4 5 0 μmol/L对两法基本无影响。 结论两种LDL C清除法测定结果的准确度和精密度均符合临床要求 ,适宜自动分析 ,值得在临床推广应用。     

卡维地洛对冠心病患者血浆氧化修饰低密度脂蛋白的影响

目的 :观察临床应用卡维地洛能否降低冠心病患者血浆氧化修饰低密度脂蛋白 (Ox LDL)水平。方法 :选择确诊冠心病患者及年龄、性别相匹配的正常对照组各 30例。冠心病组卡维地洛平均用量为 (10± 2 .5 )mg/d ,共 4个月 ,于服药前、服药后2个月及 4个月 ,分别采集清晨空腹血 ,以检测Ox LDL ,丙二醛 (MDA)。结果 :冠心病组的Ox LDL、MDA水平显著高于对照组 ,在用药后 2及 4个月冠心病组Ox LDL较用药前有显著降低 (P <0 .0 5 ) ,MDA显示出类似的趋势 (P <0 .0 1)。结论 :卡维地洛具有抗氧化作用 ,可以降低冠心病患者血浆Ox LDL水平。     

Low-density lipoprotein subfraction profiles in dialysis patients

Summary: Uraemic dyslipidaemia is a major risk factor for cardiovascular disease in end-stage renal failure patients. In patients without renal failure, high levels and qualitative abnormalities of low-density lipoprotein (LDL) are known to be atherogenic. Recently, LDL subfraction analysis has associated premature coronary artery disease with a high prevalence of small, dense LDL particles characterizing the LDL subclass phenotype B. We therefore examined the lipid profiles, LDL subfraction distribution and phenotypes in our population of haemodialysis (HD; n = 30) and peritoneal dialysis patients (PD; n = 17), and compared them to 40 asymptomatic, non-uraemic volunteers. Dialysis patients had significantly higher triglyceride and VLDL cholesterol concentrations and lower HDL cholesterol and smaller LDL peak particle diameters. PD patients had significantly higher total cholesterol, glycated haemoglobin and fasting blood glucose levels with smaller LDL peak particle diameters (24.4 [0.1] vs 24.8 [0.1 nm] than HD. Both groups showed significant negative correlations between plasma triglyceride and LDL peak particle diameter, and positive correlations between HDL cholesterol and LDL peak particle diameter. All the PD patients expressed the B phenotype (LDL peak diameter ± 25.5 nm) compared to 73% of HD patients. This study demonstrates that HD and especially PD patients have atherogenic lipid profiles which are associated with a predominance of small dense LDL particles and the highly atherogenic LDL subclass phenotype B.     

Cultured human granulosa cells as a model for corpus luteum function: relative roles of gonadotrophin and low density lipoprotein studied under defined culture conditions.

In primates, corpus luteum development involves both gonadotrophin stimulation and exposure to low density lipoprotein (LDL) delivered through vascularization of the granulosa cell-derived layer. These regulatory influences were modelled in vitro using granulosa cells obtained during in-vitro fertilization (IVF) cycles controlled with gonadotrophin releasing hormone (GnRH) analogue, human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). Granulosa cells were cultured in defined medium on extracellular matrix. Without gonadotrophin or LDL in the medium, progesterone production declined progressively. With LDL alone, there was a short-lived elevation of progesterone output which subsequently declined. Culture with HCG alone resulted in a relatively unchanged rate of steroid production over 5 days despite morphological development. This contrasted with a marked and sustained increase in progesterone output over the same time when granulosa cells were cultured with combined HCG/LDL. Cultures were challenged with combined HCG/LDL on day 5. Where initial incubation included HCG, the challenge resulted in a recovery of progesterone output to values comparable to those of granulosa cells exposed to continuous HCG/LDL. Initial incubation without gonadotrophin led to a reduced response. Results suggest that LDL delivery to granulosa cells of the early corpus luteum causes a short-lived period of progesterone production. Sustained luteinization of granulosa cells and maintenance of gonadotrophin responsiveness requires continued exposure to gonadotrophin in the luteal phase.     

接触一氧化碳工人血清LDL—C,HDL—C及脂质过氧化物含量的研究

本文对长期接触一氧化碳(CO)的工人血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、甘油三脂(TG)及脂质过氧化物(LPO)含量进行了研究。结果表明,长期接触低浓度CO者的血清TG、LPO及HbCO含量与对照组比较,有极显著性差异(P<0.001)。     

延边地区警察人群血脂水平

目的了解延边地区警察人群的血脂水平。方法将382例（男350例，女32例；朝鲜族165例，汉族217例）延边少数民族自治州公安局职工作为观察组，将100例健康人群作为对照组，应用日立7600生化分析仪分别测定甘油三酯（TG）、总胆固醇（CHO）、高密度脂蛋白胆固醇（HDL—C）、低密度脂蛋白胆固醇（LDL—C），并进行对比分析。结果观察组检出血脂异常者220例，占58．9％；对照组28例，占28％，两者差异有统计学意义（Х^2=27．78，P〈0．01），观察组明显高于对照组。此外，观察组中朝鲜族与汉族的血脂异常率差异无统计学意义（P〉0．05），但男女差异显著（P〈0．01）。结论延边地区警察人群的血脂代谢异常率明显高于普通人群，无民族差异，提示该人群应及早加强健康教育和其他预防措施。     

Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells

Low density lipoprotein (LDL) has been found to represent a suitable carrier for cytotoxic drugs that may target them to cancer. This study investigated whether very low density lipoprotein (VLDL), LDL and high density lipoprotein (HDL) can be used to effectively incorporate four cytotoxic drugs, 5-fluorouracil (5-FU), 5-iododeoxyuridine (IUdR), doxorubicin (Dox) and vindesine; characterized the complexes; and examined the effect of incorporation on drug cytotoxicity against HeLa cervical and MCF-7 breast carcinoma cells. Significant drug loading was achieved into all three classes of lipoproteins, consistent with the sizes and hydrophobicity of the drugs. The relative loading efficiency was found to be vindesine>IUdR>Dox>5-FU for all three classes of lipoproteins. As shown by electron microscopy (EM), drug incorporation did not affect the size or morphology of the lipoproteins. Differential scanning calorimetry (DSC) showed that drug loading did not significantly change the thermal transition temperature of core lipids in the lipoproteins. The transition enthalpy was changed only for LDL–Dox and LDL–vindesine. The drugs remained stable in the lipoproteins as determined by high performance liquid chromatography (HPLC). EM, DSC and HPLC data suggest that drugs were incorporated into lipoproteins without disrupting their integrity and drugs remained in their stable forms inside lipoproteins. Compared with free drugs in cytotoxicity assays, the IC₅₀ values of LDL– and HDL–drug complexes were significantly lower (2.4- to 8.6-fold for LDL complexes and 2.5- to 23-fold for HDL complexes). All free or lipoprotein-bound drug formulations were comparably more cytotoxic against MCF-7 than HeLa cells. Upregulating the lipoprotein receptors enhanced, and downregulating them inhibited, the cytotoxicity, indicating the mechanistic involvement of lipoprotein receptor pathways. Complexes of all four drugs with VLDL, in contrast to LDL and HDL, had the same cytotoxicity as the four corresponding free drugs. Our results suggest that further studies are required of the potential of HDL to be a cancer targeting drug carrier.     

Lipoprotein lipase in relation to inflammatory activity in rheumatoid arthritis

Objective. To evaluate the impact of chronic inflammation on lipoprotein lipase (LPL) levels and triglyceride metabolism in patients with rheumatoid arthritis (RA). Design. Plasma levels of LPL activity and mass before and after heparin were determined in post-menopausal women with active RA and in controls. The results were related to lipid levels and inflammatory variables. The LPL activity and mass together with triglyceride levels were also measured before and 6 h after an oral fat load. Setting. The study was performed on in- and out-patients at a University Rheumatology clinic. The controls came from the same reference area. Subjects. Altogether 17 consecutive post-menopausal female patients with RA and 16 age and sex matched controls were enrolled for the initial determination of LPL. Fifteen of the patients and 15 of the controls agreed to take part in the fat load. Of these, one patient and one control were excluded. Main outcome measures. LPL determination: basal levels and post-heparin levels of LPL activity and mass. Correlations between LPL and blood lipids (cholesterol, triglycerides), lipoprotein levels (high density lipoprotein, HDL; low density lipoprotein, LDL), erythrocyte sedimentation rate (ESR) acute phase proteins (orosomucoid, haptoglobin, fibrinogen mass) and cytokines (tumour necrosis factor α, TNF-α; interleukin 1β, IL-1β; and interleukin-6, IL-6). Fat tolerance test: LPL activity, mass and triglyceride levels before and 6 h after a per oral fat load. Results. Pre-heparin LPL mass (P<0.01) and activity (P<0.01) were significantly lower in the rheumatoid patients. Pre-heparin LPL mass showed no correlation to the lipid levels, but an inverse correlation to several inflammatory parameters; it was significant for orosomucoid (r_s=?0.63, P<0.05) and C-reactive protein (CRP) (r_s=?0.54, P<0.05) and close to significant for haptoglobin (r_s=?0.48, P=0.087) and IL-6 (r_s=?0.52, P=0.061). Six hours after a lipid load the LPL activity and mass were significantly lower in RA (P<0.05 and P<0.01, respectively) but the triglyceride level was not significantly different compared to controls. Conclusion. An inverse relationship exists between inflammatory status and pre-heparin LPL mass. Pre-heparin LPL mass reflects mainly the inactive monomeric fraction of LPL. This has been shown to hinder the uptake of remnant lipoprotein particles through competition with lipoprotein bound dimeric LPL for the LDL receptor-related protein (LRP receptor) on hepatocytes and macrophages in culture. A decrease of the level of monomeric LPL in plasma may thus be beneficial for remnant catabolism. The same mechanism may on the other hand increase macrophage uptake of lipids. This may not affect global lipid metabolism but may be important in driving the atherosclerotic process in the vessel wall.