氧化低密度脂蛋白促进血管平滑肌细胞表达基质金属蛋白酶-2

目的：用氧化低密度脂蛋白对培养的大鼠主动脉平滑肌细胞进行干预，观察其对血管平滑肌细胞表达MMP-2的影响。方法：用组织贴块法体外培养大鼠主动脉平滑肌细胞，分组后分别予以0、25μg/ml LDL，25μg/ml OX-LDL进行干预。提取细胞总RNA和总蛋白分别进行RT-PCR，western blot-ting检测，同时取出条件培养基经含1mg/ml明胶的10％聚丙烯酰胺凝胶垂直电泳行酶谱法（zymo-gra-phy）检测分泌于培养基中的MMP-2活性。结果：经mRNA、蛋白和酶活性检测，发现25μg/ml OX-LDL干预48h时，MMP-2的表达水平较对照和25μg/ml LDL明显增加。结论：OX-LDL能促进血管平滑肌细胞表达MMP-2，这提示血管细胞外基质的降解在氧化脂蛋白诱发的动脉粥样硬化斑块产生和破裂机制中起着一定作用。     

整合素CD11a、CD11b和CD11c在大鼠心脏发育中的表达变化

目的 探讨整合素CD11a、CD11b和CD11c在大鼠心脏发育中的表达变化。方法 利用免疫组织化学和RT-PCR方法,检测胚胎18d(E18d)、生后5d(P5d)、P19d、P40d及生后1年（P1y）大鼠心肌组织的CD11a、CD11b和CD11c的基因和蛋白表达。结果 免疫组织化学结果显示,大鼠心肌
组织CD11a、CD11b和CD11c表达部位在心肌细胞质内;从E18d到P1y大鼠心肌组织CD11a、CD11b和CD11c的表达逐渐减弱。 RT-PCR显示,CD11a、CD11b、CD11c各组均呈阳性表达。其中CD11a在P5d和P40d间,P5d和 P19d间比较（P>0.05）差异无统计学意义,其他各组间比较差异均有统计
学意义;CD11b在E18d、P5d、P19d和P40d分别比较（P>0.05）差异无统计学意义,其他各组差异均有统计学意义;CD11c各组间差异有统计学意义（P<0.01）。结论 CD11a、CD11b和CD11c在大鼠心肌的发育过程中出现表达量的变化,不同结构的整合素分子在心脏发育过程表现出相似的
表达规律,它们可能对心肌细胞的发育起重要的调控作用。     

尸肾移植急性排斥反应与患者淋巴细胞CD62L、CD11a、CD4、CD8表达的关系

为探讨同种异体尸肾移植排斥反应病人淋巴细胞CD62L、CD11a表达与T细胞亚群及CD4/CD8的关系和意义。利用单克隆抗体 流式细胞仪荧光免疫技术 ,测定 10例肾移植排斥反应病人术后不同时间外周血淋巴细胞CD62L、CD11a、CD4、CD8表达并计算CD4/CD8。结果 ,肾移植病人排斥反应时其CD62L (4 6 1± 18 7vs 31 3± 10 5 ,P <0 0 1)、CD11a (4 9 5±2 0 2vs 31 9± 12 4,P <0 0 1)、CD4(2 4 4± 7 7vs 17 9± 7 4,P <0 0 1)、CD8(14 7± 2 9vs 10 4± 3 2 ,P <0 0 5 )表达均较排斥前明显增加 ,抗排斥治疗后CD11a (14 8± 6 2vs 49 5± 2 0 2 ,P <0 0 1)、CD4(15 8± 6 4vs 2 4 4± 7 7,P <0 0 5 )和CD4/CD8(1 2 8± 0 6vs 1 73± 0 79,P <0 0 5 )均明显下降。CD62L变化和CD8呈明显正相关 (r=0 9779,P <0 0 5 )。认为淋巴细胞CD62L、CD11a、CD4、CD8表达及CD4/CD8与肾移植排斥反应密切相关。免疫抑制剂 ,尤其甲基强的松尤能明显抑制淋巴细胞CD11a、CD4表达和CD4/CD8比值可能是其发挥抗排斥作用的重要机制。     

氧化型低密度脂蛋白抗体对单个核细胞CD36 mRNA表达的影响

目的:通过观察氧化型低密度脂蛋白(OX-LDL)抗体对单个核细胞CD36 mRNA表达的影响,探讨OX-LDL抗体影响泡沫细胞形成的可能机制。方法:U937细胞和新西兰兔外周血单个核细胞分别被分成4组:空白对照组(普通培养基孵育)、OX-LDL刺激组(培养基中添加50μg/L的兔抗人OX-LDL多克隆抗体)、抗体干预组(培养基中添加50μg/L的兔抗人OX-LDL多克隆抗体及100μg/L的纯化人OX-LDL)及单纯抗体组(培养基中添加100μg/L的纯化人OX-LDL),经培养24 h后,利用半定量RT-PCR技术分析CD36的mRNA表达水平。结果:无论在U937细胞或兔单个核细胞中,OX-LDL刺激组及抗体干预组CD36 mRNA的表达量均显著高于对照组,而经抗体干预后,CD36 mRNA表达量在U937细胞和在兔单个核细胞分别降低了约64.80%和35.18%,种属间差异有统计学意义。结论:抗OX-LDL抗体可以抑制单个核细胞CD36抗原的表达,从而抑制泡沫细胞形成过程中OX-LDL向细胞内的聚集。     

CD11b在小鼠脾脏和淋巴结细胞中的差异表达及其功能

目的研究CD11b在小鼠脾脏和淋巴结细胞的差异表达及其生物学特性。方法流式细胞术分析CD11b在C57BL/6小鼠脾脏和淋巴结细胞、不同T细胞亚群的表达及其与T细胞活化的关系。结果 CD11b在脾脏细胞的表达(19.9±2.5)%略高于淋巴结的细胞(16.0±4.2)%(P=0.026)。脾脏中CD11b主要表达于CD3-细胞(14.93±0.94)%,淋巴结中CD11b主要表达于CD3+细胞(12.52±1.32)%;在脾脏和淋巴结T细胞亚群中,CD11b均主要表达于CD4+T细胞。进一步分析发现,CD4+CD11b+细胞高表达CD44和CD62L,且Freund完全佐剂(CFA)激活后的CD4+T细胞高表达CD11b。结论 CD11b主要表达于脾脏的非T细胞和淋巴结的T细胞。T细胞中CD11b主要表达于CD4+T亚群,且CD11b表达与T细胞活化有关。     

一氧化氮吸入对实验性胎粪吸入兔肺中性粒细胞表面CD11b表达的影响

目的 :探讨在不同氧浓度下吸入不同浓度NO治疗胎粪吸入综合征大耳白兔 ,对兔肺中的中性粒细胞表面粘附分子CD11b表达的影响。方法 :对常频通气下的胎粪吸入综合征家兔分别在 2 1% ,10 0 %氧浓度下给予0 2× 10 -6 mol/L ,0 3 3× 10 -6 mol/L ,0 67× 10 -6 mol/LNO治疗 12h ,通过左颈总动脉插管检测平均动脉压 ,血液高铁血红蛋白含量的变化。并采用流式细胞术检测肺泡灌洗液中中性粒细胞表面粘附分子CD11b的平均荧光强度。结果 :各组动物在各时间点平均动脉血压无差别。在两种氧浓度不同NO吸入浓度下血液各时点高铁血红蛋白含量在正常范围之内。不同氧浓度下 ,0 3 3× 10 -6 ,0 67× 10 -6 mol/LNO吸入治疗组肺泡灌洗液中的中性粒细胞上粘附分子CD11b的表达比非干预组要低 (平均数±标准差 :2 1%O2 ,0 3 3× 10 -6 mol/LNO ,12 1± 2 0vs 3 92± 2 0 4,0 67×10 -6 mol/LNO ,112± 3 0vs 3 92± 2 0 4;10 0 %O2 ,0 3 3× 10 -6 mol/LNO ,113± 2 4vs 2 93± 65 ,0 67× 10 -6 mol/LNO ,10 2±114vs 2 93± 65 ,P <0 0 5 ) ;0 2× 10 -6 mol/LNO吸入治疗组对粘附分子的表达无影响。 (平均数±标准差 :2 1%O2 ,190± 10 1vs 3 92± 2 0 4;10 0 %O2 ,2 2 2± 85vs 2 93± 65 ;P >0 0 5 ) ;同     

Pam3CSK4对血小板活化及其TLR2表达的影响

Objective To investgate role of TLR2 in the activation, the innate immune and inflammation of human platelets. Methods Human washed platelets were separated from healthy people(n=5) and were stimulated with different concentrations(1μg/ml, 5μg/ml, 10μg/ml) of TLR2 agonistPam3CSK4(a synthetic bacterial lipoproteins). Then the platelet aggregation rate, the expression of CD62p and TLR2 on the platelet surface were measured. Results The platelet aggregation rate were (28.32±5.67)%, (52.56±8.54)% and (76.24±11.23)%, respectively, at concentration of 1μg/ml, 5μg/mland 10μg/ml of Pam3CSK4, more than (12.83±2.43)% at 0μg/ml of it. In addition, the expression of CD62p were (18.45±2.66)%, (22.45±2.04)%, (29.53±4.08)%, respectively at above concentration of Pam3 CSK4, more than (11.20±1.67)% of CD62p at control group(P<0.01). The expression of TLR2 was not significantly increased at a lower concentration of Pam3CSK4(1μg/ml) with (16.85±6.10)% compared with(10.81±3.99)% at the control group. However, it were (21.15±9.90)% and (22.52±9.26)%, respectively, at a higher concentration(5μg/ml, 10μg/ml)more than(10.81±3.99)% at the control group(P<0.05). Conclusion Pam3CSK4 induce aggregation, activation and the up-regulation of TLR2 of platelet by stimulating TLR2 receptor of it. Thereafter, TLR2 play an important role in the innate immune of platelet.     

CD4~+CD25~+调节性T细胞活化对CCR4/CCR5膜表达及功能的影响

目的探讨CD3/CD28抗体包被磁珠刺激活化的小鼠CD4+CD25+调节T细胞(Treg)表面趋化因子受体CCR4/CCR5表达及免疫抑制功能变化。方法采用磁性激活细胞分离器(MACS)纯化C57BL/6小鼠脾细胞中的CD4+CD25+T细胞,采用CD3/CD28抗体包被磁珠与鼠重组白细胞介素2刺激0、2、4 d后,流式细胞仪检测CCR4与CCR5的表达,3H-TdR掺入法检测细胞增殖活性。结果活化的CD4+CD25+T细胞CCR4的表达率明显高于CD4+CD25-T细胞对照组,CCR5的表达率明显低于对照组细胞。CD4+CD25+调节T细胞CCR4、CCR5的表达随活化时间延长持续增强,CD4+CD25-T细胞CCR5表达则逐渐减弱、CCR4表达无显著变化。活化的CD4+CD25+T细胞可明显抑制CD4+CD25-T细胞增殖,当比值为1∶1时抑制率达88.4%。结论 CD3/CD28抗体包被磁珠刺激可以增强CD4+CD25+T细胞膜表面CCR4、CCR5表达;活化CD4+CD25+T细胞免疫抑制功能强于新鲜分离的CD4+CD25+T细胞。     

Pam3CSK4对血小板活化及其TLR2表达的影响

Objective To investgate role of TLR2 in the activation, the innate immune and inflammation of human platelets. Methods Human washed platelets were separated from healthy people(n=5) and were stimulated with different concentrations(1μg/ml, 5μg/ml, 10μg/ml) of TLR2 agonistPam3CSK4(a synthetic bacterial lipoproteins). Then the platelet aggregation rate, the expression of CD62p and TLR2 on the platelet surface were measured. Results The platelet aggregation rate were (28.32±5.67)%, (52.56±8.54)% and (76.24±11.23)%, respectively, at concentration of 1μg/ml, 5μg/mland 10μg/ml of Pam3CSK4, more than (12.83±2.43)% at 0μg/ml of it. In addition, the expression of CD62p were (18.45±2.66)%, (22.45±2.04)%, (29.53±4.08)%, respectively at above concentration of Pam3 CSK4, more than (11.20±1.67)% of CD62p at control group(P<0.01). The expression of TLR2 was not significantly increased at a lower concentration of Pam3CSK4(1μg/ml) with (16.85±6.10)% compared with(10.81±3.99)% at the control group. However, it were (21.15±9.90)% and (22.52±9.26)%, respectively, at a higher concentration(5μg/ml, 10μg/ml)more than(10.81±3.99)% at the control group(P<0.05). Conclusion Pam3CSK4 induce aggregation, activation and the up-regulation of TLR2 of platelet by stimulating TLR2 receptor of it. Thereafter, TLR2 play an important role in the innate immune of platelet.     

重症烧伤休克大鼠白细胞表面beta-2整合素的表达

目的 :阐明烧伤休克时 beta-2整合素与白细胞 -内皮细胞粘附间的关系。方法 :将 16只 SD大鼠随机均分为对照组和烧伤休克组。应用流式细胞技术检测中性粒细胞及单细胞表面 beta-2整合素CD11a( LFA-1)和 CD11b( Mac-1)的表达量变化 ,同时比较观察二组动物肠系膜微循环中微静脉内白细胞与内皮细胞粘附数量变化。结果 :二组自身对照 (烫伤前与烫伤后 3 h或开腹前与开腹后 3 h)及相互对比结果显示 ,中性粒细胞及单核细胞表面 CD11a表达量均无显著差异 ( P>0 .0 5 ) ;在烧伤组 ,单核细胞 CD11b有显著降低( P<0 .0 5 ) ,而中性粒细胞 CD11b有显著升高 ( P<0 .0 5 )。微循环观察结果显示 ,休克组动物烫伤后随时程延长附壁滚动及紧密粘附的白细胞数量明显增多 ,而对照组则无明显变化。结论 :烧伤休克状态下 ,白细胞表面 CD11a数量无显著变化 ,而 CD11b数量则有所改变。白细胞 -内皮细胞粘附力的增强可能有 beta-2整合素功能活性上调参与。     

脂蛋白和C反应蛋白对单核细胞趋化蛋白-1的影响

目的探讨单核细胞趋化蛋白-1（MCP-1）及其受体趋化因子受体2（CCR-2）经动脉粥样硬化相关因素刺激后表达量的变化情况。方法密度梯度离心法从健康成人外周血中分离获得单个核细胞，体外培养48h。给予氧化低密度脂蛋白（ox-LDL）、C反应蛋白（CRP）及高密度脂蛋白（HDL）进行干预。干预后用实时荧光定量RT—PCR技术检测单核细胞MCP-1 mRNA和CCR2 mRNA的含量，ELISA法检测MCP-1蛋白含量。结果ox—LDL＋CRP组、ox—LDL、CRP处理组MCP-1和CCR2 mRNA表达水平和MCP—1蛋白含量明显高于对照组（P〈0．05）。而经HDL处理的单核细胞表达MCP-1和CCR2 mRNA水平下调，MCP-1蛋白含量低于对照组（P〈0．05）。结论在体外培养的条件下，CRP和ox-LDL可以促进MCP-1和CCR2 mRNA表达，继而导致MCP-1含量增加，增强炎症反应的范围和强度。HDL可以有效的抑制MCP-1的表达。     

C-reactive protein (CRP) induces chemokine secretion via CD11b/ICAM-1 interaction in human adherent monocytes

Several studies support C-reactive protein (CRP) as a systemic cardiovascular risk factor. The recent detection of CRP in arterial intima suggests a dual activity in atherosclerosis as a circulating and tissue mediator on vascular and immune cells. In the present paper, we focused on the inflammatory effects of CRP on human monocytes, which were isolated by Ficoll-Percoll gradients and cultured in adherence to polystyrene, endothelial cell monolayer, or in suspension. Chemokine levels, adhesion molecule, and chemokine receptor expression were detected by ELISA, flow cytometry, and real-time RT-PCR. Migration assays were performed in a Boyden chamber. Stimulation with CRP induced release of CCL2, CCL3, and CCL4 in adherent monocytes through the binding to CD32a, CD32b, and CD64, whereas no effect was observed in suspension culture. This was associated with CRP-induced up-regulation of adhesion molecules membrane-activated complex 1 (Mac-1) and ICAM-1 on adherent monocytes. Blockade of Mac-1/ICAM-1 interaction inhibited the CRP-induced chemokine secretion. In addition, CRP reduced mRNA and surface expression of corresponding chemokine receptors CCR1, CCR2, and CCR5 in adherent monocytes. This effect was a result of chemokine secretion, as coincubation with neutralizing anti-CCL2, anti-CCL3, and anti-CCL4 antibodies reversed the effect of CRP. Accordingly, a reduced migration of CRP-treated monocytes to CCL2 and CCL3 was observed. In conclusion, our data suggest an in vitro model to study CRP activities in adherent and suspension human monocytes. CRP-mediated induction of adhesion molecules and a decrease of chemokine receptors on adherent monocytes might contribute to the retention of monocytes within atherosclerotic lesions and recruitment of other circulating cells.     

The effects of different lipoproteins on cholesterol metabolism in smooth muscle cells of rabbit aorta]

In the present experiment, M-SMC were cultured from rabbit aorta by an explant method and I-SMC cultured by the explant method from cannulated aortic intima of rabbits, and the effects of LDL, A-LDL, OX-LDL and HDL on the cholesterol metabolism in both types of cells were investigated by using 14C oleic acid as the source of cholesterol re-esteri fication in cells. The results showed that LDL enhanced cholesterol re-esterification in both types of cells and HDL had an opposite effect, A-LDL could increase CE synthesis only in I-SMC, while OX-LDL showed a complex effect on the level of CE in different cells by different concentration. The present experiment has studied the relationship between lipoprotein and cholesterol metabolism in SMC at the level of cell metabolism, and suggests that lipoproteins play a key role in AS.     

Antigens and granularity of blood monocytes in relation to inflammatory markers and lipids in postmenopausal women

OBJECTIVES: The menopause is associated with an increase of inflammatory markers (C-reactive protein, fibrinogen), cytokines (INFgamma, TNF, etc.) and blood lipoproteins. In vitro, CRP, LDL and fibrinogen can modulate or potentiate interleukines production by monocytes. The aim of this work was to study, the relationships in vivo between hs-CRP, fibrinogen, lipoproteins and the phenotype of circulating monocytes. METHODS: The monocytes phenotype, in postmenopausal women (n=26) without history of cardiovascular disease, was determined, by flow cytometry, measuring granularity and CD14, HLA-DR and CD62-L antigens expression. Blood monocytes were divided in CD14+dim monocytes (low CD14 expression) and CD14+bright monocytes (high CD14 expression). RESULTS: HLA-DR was negatively correlated with hs-CRP and fibrinogen. The relationships between ApoB, LDL/ApoB ratio and CD14 expression was restricted to the CD14+bright monocytes. Blood lipids, i.e. total cholesterol, LDL-c and ApoB were correlated with the granularity of both subsets. CD14+dim monocytes were characterized by a low granularity and CD62-L expression. CONCLUSIONS: Our data show that fibrinogen and hs-CRP are correlated with a reduced antigen-presenting capacity. Expression of CD14 on CD14+bright monocytes is negatively associated to atherogenic LDL. Blood monocytes granularity was positively correlated with serum lipids indicating that monocytes could uptake modified LDL in circulation and not restricted to subendothelial space.     

Lipopolysaccharide is transferred from high-density to low-density lipoproteins by lipopolysaccharide-binding protein and phospholipid transfer protein

Lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria, is a potent endotoxin that triggers cytokine-mediated systemic inflammatory responses in the host. Plasma lipoproteins are capable of LPS sequestration, thereby attenuating the host response to infection, but ensuing dyslipidemia severely compromises this host defense mechanism. We have recently reported that Escherichia coli J5 and Re595 LPS chemotypes that contain relatively short O-antigen polysaccharide side chains are efficiently redistributed from high-density lipoproteins (HDL) to other lipoprotein subclasses in normal human whole blood (ex vivo). In this study, we examined the role of the acute-phase proteins LPS-binding protein (LBP) and phospholipid transfer protein (PLTP) in this process. By the use of isolated HDL containing fluorescent J5 LPS, the redistribution of endotoxin among the major lipoprotein subclasses in a model system was determined by gel permeation chromatography. The kinetics of LPS and lipid particle interactions were determined by using Biacore analysis. LBP and PLTP were found to transfer LPS from HDL predominantly to low-density lipoproteins (LDL), in a time- and dose-dependent manner, to induce remodeling of HDL into two subpopulations as a consequence of the LPS transfer and to enhance the steady-state association of LDL with HDL in a dose-dependent fashion. The presence of LPS on HDL further enhanced LBP-dependent interactions of LDL with HDL and increased the stability of the HDL-LDL complexes. We postulate that HDL remodeling induced by LBP- and PLTP-mediated LPS transfer may contribute to the plasma lipoprotein dyslipidemia characteristic of the acute-phase response to infection.     

High-density lipoprotein binding rate differs greatly between genotypes 1b and 2a/2b of hepatitis C virus

The hepatitis C virus (HCV) virion is associated with lipoproteins and immunoglobulins in the sera of patients with chronic hepatitis C; however, an accurate binding rate of HCV to lipoproteins or immunoglobulins has not yet been elucidated. Therefore, the accurate binding rate of HCV to low-density lipoproteins (LDL), high-density lipoproteins (HDL), and immunoglobulins was measured quantitatively by a real-time PCR assay. The immunoglobulin binding rate of HCV was found to be greater than 97.5% in most patients, as compared with an LDL binding rate of greater than 80% in most patients. In contrast, the HDL binding rate was greater than 98% in the genotype 2a/2b patients, while it varied in the genotype 1b patients. The genotype 2a/2b HCV not only had a higher LDL binding rate but also had a strikingly higher HDL binding rate than that of the genotype 1b HCV. These lipoprotein binding rates correlated neither to any patient's variables, including the serum apolipoprotein levels, nor to the viral load or the hypervariable region 1 (HVR 1) amino acid sequences. Most of the HCV virions in the sera of such patients have been shown to be associated simultaneously with immunoglobulins and LDL and/or HDL, but not exclusively.     

The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury.

The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel-exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low-density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions.     

Direct modulatory effect of C-reactive protein on primary human monocyte adhesion to human endothelial cells

C-reactive protein (CRP) is the prototypic acute phase serum protein in humans. The effects of CRP on primary human monocyte adhesion molecule expression and interaction with the endothelium have not been studied. Herein, we describe an investigation into the phenotypic and functional consequences of CRP binding to peripheral blood monocytes ex vivo. Peripheral whole blood was collected from healthy, non-smoking males. Mononuclear cells (MNC) and monocytes were isolated by differential centrifugation using lymphoprep and Dynal negative isolation kit, respectively. Cells were exposed to CRP from 0 to 250 micro g/ml for 0-60 min at 37 degrees C and analysed for (a) CD11b, PECAM-1 (CD31) and CD32 expression by flow cytometry and (b) adhesion to LPS (1 micro g/ml; 0-24 h) treated human umbilical vein endothelial cells (HUVEC). CD14+ monocyte expression of CD11b increased significantly up to twofold when exposed to CRP, compared to controls. There was no significant difference in CD32 expression, whereas CD31 expression decreased after exposure to CRP. CRP treatment of monocytes inhibited their adhesion to early LPS-activated HUVEC (0-5 h). However, the adhesion of CRP-treated monocytes to HUVEC was significantly greater to late activation antigens on HUVEC (24 h, LPS) compared to controls. We have shown that CRP can affect monocyte activation ex vivo and induce phenotypic changes that result in an altered recruitment to endothelial cells. This study provides the first evidence for a further role for C-reactive protein in both monocyte activation and adhesion, which may be of importance during an inflammatory event.     

Impact of hormone replacement therapy on postprandial lipoproteins and lipoprotein(a) in normolipidemic postmenopausal women

In 43 normolipidemic postmenopausal women we studied fasting and postprandial (oral fat load with 50 g fat per square meter; blood sampling for 5 h) lipoprotein components and lipoprotein(a) levels before and with the administration of conjugated equine estrogens opposed by medrogestone (on days 11–21). Data was compared intraindividually; the second testing was performed during the last 5 days of the combined estrogen/progestogen phase of the third cycle. Fasting low-density lipoprotein (LDL) and total cholesterol concentrations decreased significantly; high-density lipoprotein (HDL) cholesterol, including subfractions HDL₂ and HDL₃, was not changed. Fasting triglyceride concentrations increased. All lipoprotein fractions measured showed a postprandial elevation with the exception of chylomicron cholesterol concentrations. There was a significant effect of hormone replacement therapy on the postprandial course of total cholesterol (decrease; P < 0.001), VLDL cholesterol (increase; P = 0.025), and the triglyceride proportion in the LDL plus HDL fraction (increase; P < 0.001). With hormone replacement therapy the postprandial curve of total triglycerides was increased only 1 h after the fat load while chylomicron triglyceride concentrations were lowered after 5 h. VLDL triglycerides were not influenced. In all patients with lipoprotein(a) levels above 10 mg/dl, this parameter decreased (about 25%). Although increasing fasting triglyceride concentrations, hormone replacement therapy does not bring about an exaggerated postprandial increase in triglycerides. Postprandial chylomicron clearance is evidently promoted. Hormone replacement therapy leads to a small increase in triglycerides in the LDL plus HDL fraction by inhibiting hepatic lipase activity. Moreover, the decrease in lipoprotein(a) levels may contribute to the antiatherosclerotic effect.Abbreviations: CEE conjugated equine estrogens - HDL high-density lipoproteins - HRT hormone replacement therapy - LDL low-density lipoproteins - TG triglycerides - VLDL very low density lipoproteins Correspondence to: U. Julius     

Effects of transdermal estrogen replacement therapy on plasma levels of nitric oxide and plasma lipids in postmenopausal women

OBJECTIVE: Our purpose was to assess the effects of transdermal estrogen replacement therapy (TERT) on plasma levels of nitric oxide (NO) and plasma lipids in postmenopausal women. MATERIALS AND METHODS: The study designed as a randomized, double-blind, placebo-controlled trial, involved 43 postmenopausal healthy women who had previously undergone hysterectomy. Women received either transdermal 100 microg 17beta-estradiol (Climara forte TTS) or placebo once a week for 3 months. Plasma levels of NO metabolites, estradiol (E2), total cholesterol (TC), triglicerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), HDL2 and HDL3 were measured in blood samples of all women which were collected before, after 24 h and after 3 months of therapy. RESULTS: We found significantly increased NO levels 24 h after therapy in TERT group. Moreover significantly higher NO levels were determined at 3rd month of therapy. Serum HDL and HDL2 levels of ERT group were significantly increased at 3rd month of therapy. Alteration of serum levels of HDL3, LDL and TC were not significantly different in groups. TG levels were significantly decreased in TERT group. DISCUSSION: NO-related mechanism may help to explain the cardio-protective effect of TERT in the postmenopausal period. TERT seems to have favorable effects on plasma lipids in surgical menopausal women.