冠心病患者不同类型血清氧化型低密度脂蛋白和高敏C反应蛋白水平的差异

目的比较血清氧化型低密度脂蛋白、高敏C反应蛋白水平在不同类型冠心病中的差异。方法检测了82例冠心病患者(急性冠状动脉综合征42例、稳定型心绞痛20例和陈旧性心肌梗死20例)和22例正常对照者血清氧化型低密度脂蛋白、高敏C反应蛋白、高密度脂蛋白胆固醇、总胆固醇和高密度脂蛋白胆固醇水平,并比较各指标水平在不同类型冠心病中的差异。结果血清氧化型低密度脂蛋白水平在冠心病组明显高于对照组(62.5±24.8μg/L比42.3±17.9μg/L,P<0.05),在急性冠状动脉综合征组明显高于稳定型心绞痛组和陈旧性心肌梗死组(68.9±23.4μg/L比41.5±21.3μg/L和50.5±21.6μg/L,P<0.05);血清高敏C反应蛋白水平在冠心病组明显高于对照组(15.58±4.32mg/L比6.94±1.93mg/L,P<0.05),在急性冠状动脉综合征组明显高于稳定型心绞痛组和陈旧性心肌梗死组(19.31±1.43mg/L比10.29±1.01mg/L和9.56±1.72mg/L,P<0.05);血清低密度脂蛋白胆固醇水平在冠心病组明显高于对照组(3.46±1.11mmol/L比2.87± 0.82mmol/L,P<0.05),但在急性冠状动脉综合征组与稳定型心绞痛组和陈旧性心肌梗死组差异无显著性(3.64±0.85mmol/L比3.06±1.23mmol/L和3.40±1.35mmol/L);血清总胆固醇/高密度脂蛋白胆固醇比值在冠心病组明显高于对照组(3.46±1.11比2.87±0.82,P<0.05),在不同类型冠心病中亦有差异(P<0.05)。结论血清氧化型低密度脂蛋白和高敏C反应蛋白水平及总胆固醇/高密度脂蛋白胆固醇比值在冠心病不同类型中有差异,可能为诊断冠心病的指标。     

LPL基因旁侧区域内多态性与高血压病或血压数量性状的连锁分析

目的　绝大多数高血压病患者都伴有血脂代谢异常 ,而且高血压在具有家族性混合型高脂血症的家庭中发生频率更高。由此认为 ,血压调节和血脂代谢可能存在共同的遗传基础。本研究旨在探讨脂蛋白脂酶 (LPL)基因是否为国人高血压病发生的易感基因。方法　筛选了 1 4 8个高血压病家系 ,使用ABITM377测序仪 ,结合GENESCAN技术对LPL基因旁侧区域内 7个多态性进行基因型检测。使用S .A .G .E/SIBPAL2和SOLAR程序完成血压质量和数量性状的弱参数连锁分析 ,使用TDT/STDT进行连锁不平衡分析。所有分析均对年龄、性别和体重指数进行了校正。结果　 (1 )使用SOLAR程序 ,连锁分析提示D8S2 6 1与收缩压连锁 (LOD =2 5 2 )。使用LOD值拟合分析 (1 00 0 0次 ) ,进一步证实D8S2 6 1与收缩压连锁 (P =0 0 0 0 1 )。 (2 )使用S .A G E/SIBPAL2程序观察到D8S1 1 4 5 (P =0 0 0 97)、D8S5 1 1 (P =0 0 0 36 )和D8S5 6 0 (P =0 0 1 1 5 )与高血压连锁 ;D8S2 6 1和NEFL分别与收缩压和舒张压均连锁。 (3)TDT/STDT分析提示D8S2 6 1的第三等位基因与高血压存在连锁不平衡 (χ2 =8 6 4 3,P <0 0 1 ;Z′ =2 4 0 8,P <0 0 5 ) ,Bonferroni校正值Z′ =3 5 1 7,P <0 0 1。结论LPL基因旁侧区域内的某些基因或LPL基因本身可能参与     

Elevated lipoprotein (a) levels are associated with the presence and severity of coronary artery disease in patients with type 2 diabetes mellitus

Background and aims

The role of lipoprotein (a) [Lp(a)] in coronary artery diseases (CAD) with special clinical background such as type 2 diabetes mellitus (T2DM) has not been fully determined. The aim of the present study was to investigate the relation of Lp(a) to type 2 diabetic patients with or without CAD.

肺炎心力衰竭患儿血清脂蛋白(a)和D-二聚体的变化

目的 :了解支气管肺炎并心力衰竭 (简称肺炎心衰 )患儿血清脂蛋白 (a) [Lp(a) ]和D 二聚体 (D D)浓度变化的临床意义。方法 :采用ELISA法测定肺炎心衰、普通肺炎患儿、健康儿童 (对照组 )血清Lp(a)和D D浓度。结果 :肺炎心衰、普通肺炎患儿血清Lp(a)逐渐下降 ,两两比较差异均有显著性意义 ;肺炎心衰组血D D较普通肺炎组和对照组的明显增高 ,而后两组的差异无显著性意义 ;肺炎心衰组治疗后血D D和Lp(a)均明显下降 ,差异均有显著性意义。肺炎心衰患儿血清Lp(a)与血浆D D呈正相关。 结论 :支气管肺炎及肺炎心衰婴幼儿血清Lp(a)增高可能参与病理生理的过程 ,血Lp(a)和血浆D D水平可作为肺炎心衰病情预后的判断指标     

非对称二甲基精氨酸促进大鼠主动脉氧化型低密度脂蛋白受体表达

目的观察非对称二甲基精氨酸对大鼠主动脉氧化型低密度脂蛋白受体表达的影响,探讨其在动脉粥样硬化中的作用。方法健康成年Wistar大鼠34只随机分为四组:①对照组(n=7)正常饲料喂养,正常饮水。②高脂饲料组(n=9)用高脂饲料喂养,正常饮水。③非对称二甲基精氨酸(简称甲基精氨酸)组(n=9)用高脂饲料喂养,饮水中按体重加入非对称二甲基精氨酸[0.2 mg/(kg.d)]。④L精氨酸组(n=9)用高脂饲料喂养,饮水中按体重加入非对称二甲基精氨酸[0.2 mg/(kg.d)]和L精氨酸[12 mg/(kg.d)]。18周后麻醉大鼠,取主动脉,以RT-PCR和Western blotting检测主动脉氧化型低密度脂蛋白受体mRNA和蛋白表达。结果①甲基精氨酸组氧化型低密度脂蛋白受体mRNA表达量(1.608±0.114)较对照组(0.363±0.027)和高脂饲料组(0.480±0.065)增加(P均<0.001),L精氨酸组氧化型低密度脂蛋白受体mRNA表达量(0.902±0.037)较甲基精氨酸组降低(P<0.01);②甲基精氨酸组氧化型低密度脂蛋白受体蛋白表达量(0.662±0.063)较对照组(0.111±0.022)和高脂饲料组(0.251±0.004)增加(P均<0.001),L精氨酸组(0.364±0.117)较甲基精氨酸组氧化型低密度脂蛋白受体蛋白表达降低(P<0.05)。结论非对称二甲基精氨酸促进大鼠主动脉氧化型低密度脂蛋白受体基因和蛋白表达,可能与非对称二甲基精氨酸促进动脉粥样硬化有关。     

Maternal dietary ethanol consumption is associated with hypertriglyceridemia in adult rat offspring

BACKGROUND: The consumption of significant amounts of alcohol (ethanol, EtOH) may markedly increase serum triglyceride levels. This study describes a significant increase in fasting serum triglyceride (TG) levels in adult male rats whose mothers consumed EtOH. The hypertriglyceridemia occurred although the offspring never directly consumed EtOH and had consumed only rat chow for the preceding 14 months. Furthermore, both male and female adult offspring had an additional, significant increase in TG levels if their mothers consumed EtOH and experienced stress (restraint) during the pregnancy. METHODS: Harlan-derived Sprague Dawley female rats were dosed during pregnancy with EtOH via a liquid diet, and their offspring were compared with offspring of mothers who were either fed ad libitum or pair-fed the liquid diet without EtOH. At birth, the offspring of EtOH mothers exhibited no visible abnormalities except reduced weight, and all offspring were surrogate fostered within 48 hr of birth to mothers who had consumed commercial rat chow throughout their pregnancy. After weaning, all offspring consumed only commercial rat chow, and they were examined over the next 14 months for changes in triglyceride homeostasis as a function of maternal alcohol intake. RESULTS: Adult male offspring of mothers that consumed EtOH during their pregnancy had significant increases in fasting serum triglycerides associated with an increase in the very low density lipoprotein serum fraction. Acute administration of insulin to the offspring of all maternal dietary groups resulted in a rapid clearing of the serum triglycerides, and there were no differences in basal or heparin-releasable lipoprotein lipase activity between any of the progeny. Castration of the male offspring of EtOH-treated mothers prevented the development of elevated TG levels. Administration of testosterone to littermate female offspring increased circulating TG levels compared with testosterone-treated offspring of pair-fed mothers. EtOH-consuming mothers who also underwent five periods of restraint-induced stress (approximately 10 min each session) produced offspring whose fasting serum TG levels were higher than those whose mothers consumed EtOH but experienced no restraint or who experienced restraint but no EtOH. Maternal stress significantly reduced lipoprotein lipase activity in some offspring treatment groups, but the changes did not correspond to changes in the serum TG levels of the offspring. That is, maternal restraint-induced stress was associated with a loss of heparin-releasable lipoprotein lipase activity by male progeny from pair-fed and EtOH-fed mothers and the female offspring of ad libitum-fed and EtOH-fed mothers. CONCLUSIONS: Although serum triglycerides increased with age in all offspring, the increase was much more pronounced in the progeny of mothers who consumed EtOH during their pregnancy. The hypertriglyceridemia was significantly more pronounced in the male offspring and in female offspring treated with testosterone. Castration of male offspring inhibited the hypertriglyceridemia development, which suggests that male sex hormones may play a role in the development of this condition. Maternal EtOH consumption coupled with maternal restraint-induced stress significantly increased the level of hypertriglyceridemia in both male and female offspring compared with offspring whose mothers experienced restraint but no EtOH or EtOH with no restraint. If this study models the human condition, the results could represent an unrecognized risk factor in a number of adult disease states hypothesized to be associated with hypertriglyceridemia, such as cardiovascular disease, hypertension, and diabetes.     

单核细胞趋化蛋白-1及脂蛋白(a)与梅尼埃病关系的研究

目的探讨单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)及脂蛋白(a)[lipoprotein(a),LP(a)]与梅尼埃病的关系。方法选取30只健康SD大鼠,分成正常组、对照组及实验组,每组10只,实验组腹腔注射醋酸去氨加压素(4μg·kg^-1·d^-1连续注射7 d后改为6μg·kg^-1·d^-1连续注射3 d)行膜迷路积水造模,对照组腹腔注射等量生理盐水,正常组不作处理,停药7 d后对三组动物行ABR检测,取耳蜗中阶横截面积(SM)/(中阶+前庭阶横截面积)(SM+SV)比值评价膜迷路积水情况。造模成功后通过免疫组化染色检测耳蜗组织中MCP-1的表达,通过酶联免疫吸附实验(ELISA)法检测血清中LP(a)的水平,对LP(a)水平与内耳积水程度及大鼠ABR各指标进行相关性分析。结果实验组波Ⅱ阈值升高、波Ⅱ、Ⅴ潜伏期及Ⅲ-Ⅴ波间期较正常组和对照组均延长,差异有统计学意义(P<0.05)。实验组、对照组、正常组SM/(SM+SV)比值分别为0.45±0.04、0.34±0.02、0.35±0.01,前者显著大于后两者(P<0.05)。实验组MCP-1在耳蜗螺旋器、血管纹螺旋韧带及神经节细胞组织表达明显,前庭膜上也有表达,其它两组无表达。实验组、对照组、正常组LP(a)水平分别为4.07±0.20、1.36±0.12、1.38±0.14 mg/L,前者显著高于后两者(P<0.001),LP(a)表达水平与膜迷路积水程度及ABR各指标间均呈正相关(P<0.001)。结论膜迷路积水模型大鼠耳蜗组织中MCP-1表达明显,血清LP(a)水平明显升高,且LP(a)水平与膜迷路积水程度及大鼠听力下降呈正相关,提示MCP-1和LP(a)可能与梅尼埃病的发生有关。     

Flow-mediated dilation,carotid wall thickness and HDL function in subjects with hyperalphalipoproteinemia

Background and aimsThe relationships between very high plasma HDLc and subclinical atherosclerosis are still a matter of debate.Methods and resultsTwenty subjects with primary hyperalphalipoproteinemia (HAL, with HDLc in the highest 10th percentile and absence of overt secondary causes of this condition), aged 30–65 years, were compared with 20 age and sex-matched controls. Lipid determination, lipoprotein particle distribution (Lipoprint^®), Cholesterol Efflux Capacity (CEC), plasma adhesion molecule, analyses of CETP, SRB1 and LIPG genes and of different markers of subclinical vascular disease (ankle-brachial index, ABI; carotid intima-media thickness, cIMT; brachial-artery flow mediated dilation, FMD) were performed. Fasting HDLc levels were 40 mg/dl higher in HAL subjects while LDLc concentration was comparable to control group. CETP gene analysis in HAL subjects identified one novel rare Single Nucleotide Polymorphism (SNP, Asp131Asn), possibly damaging, while the common SNP p.Val422Ile was highly prevalent (50% vs. 27.4% in a control population). No rare mutations associated with HAL were found in SR-B1 and LIPG genes. Polyacrylamide gel electrophoresis in HAL subjects disclosed larger and more buoyant HDL particles than in controls, while LDL profile was much more similar. ABI, cIMT and arterial plaques did not differ in cases and controls and the two groups showed comparable FMD at brachial artery examination. Similarly, ABCA1 and ABCG1 HDL-mediated CEC, the most relevant for atheroprotection, did not discriminate between the groups and only ABCG1 pathway seemed somewhat related to arterial reactivity.ConclusionsHDL dimension, function and genetics seem scarcely related to subclinical atherosclerosis and vascular reactivity in middle-aged HAL subjects.     

Type 1 hyperlipoproteinemia due to a novel deletion of exons 3 and 4 in the GPIHBP1 gene

Objectives

Type 1 hyperlipoproteinemia is an autosomal recessive disorder characterized by severely elevated plasma triglyceride levels, which may lead to abdominal pain and pancreatitis, eruptive xanthomas and failure to thrive. Mutations in the genes encoding lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), lipase maturing factor 1 (LMF1) or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) have been found to cause Type 1 hyperlipoproteinemia.

Methods

Two sibpairs belonging to two different branches of an extended pedigree were referred for molecular elucidation for their increased plasma triglyceride levels, which untreated were >27 mmol/L. The genes LPL, APOC2, APOA5, LMF1 and GPIHBP1 were analyzed by DNA sequencing.

Results

No mutations were found in LPL, APOC2, APOA5 or LMF1. No PCR products were obtained for exons 3 and 4 of GPIHBP1 from DNA of the 4 affected subjects. Subsequent long-range PCR revealed that the four affected were homozygous for a deletion comprising exons 3 and 4 of GPIHBP1. No increase in LPL activity was found in post-heparin plasma from the subjects.

Conclusion

Homozygosity for a deletion of exons 3 and 4 of GPIHBP1 results in Type 1 hyperlipoproteinemia.     

Effect of Nicotinic acid/Laropiprant in the lipoprotein(a) concentration with regard to baseline lipoprotein(a) concentration and LPA genotype

Background

Lipoprotein(a) [Lp(a)] is a lipoprotein in which apolipoproteinB-100 is linked to apolipoprotein(a) [apo(a)]. Significant variation in Lp(a) concentration is specific to LPA gene, which codes for apo(a). Nicotinic acid (NA) is used for treatment of dyslipidemias, and the lowering effect of NA on Lp(a) has been previously reported.

Objective

To evaluate the Lp(a) lowering effect of 1 g/20 mg and 2 g/40 mg day of Nicotinic acid/Laropiprant in subjects with different baseline Lp(a) concentrations and depending on the LPA genotype.

Methods

In an open-label, 10-week study, 1 g/20 mg day of NA/Laropiprant for 4 weeks followed by 6 weeks of 2 g/40 mg day conducted at 3 centers in Spain, 82 subjects were enrolled. Patients were studied at baseline and at the end of both treatment periods and were enrolled in three groups: normal Lp(a) (< 50 mg/dL), high Lp(a) (50–120 mg/dL) and very high Lp(a) (> 120 mg/dL). The LPA genetic polymorphism was analyzed by a real-time PCR.

Results

There was a significant difference in LPA genotypes among Lp(a) concentration groups and an inverse and significant correlation between baseline Lp(a) concentration and LPA genotype was found (R = − 0.372, p < 0.001). There were a significant decrease in total cholesterol, triglycerides, LDL cholesterol, apo B and Lp(a), and a significant increase in HDL cholesterol after NA/Laropiprant treatment, without changes in BMI. However, there were no statistical differences in percentage variation of analyzed variables depending on LPA genotype.

Conclusion

LPA genotype is a major determinant of Lp(a) baseline concentration. However, the lipid lowering effect of NA is not related to LPA genotype.