Vascular protection by high-density lipoprotein-associated sphingosine-1- phosphate

Epidemiological studies and animal experiments have consistently demonstrated cardiovascular protection by high-density lipo-protein (HDL). Findings from a growing number of studies further indicate that sphingosine-1-phosphate (S1P) mediates many of the beneficial effects of HDL on the cardiovascular system, including vasodilatation, angiogenesis, maintenance of endothelial barrier function, and protec?tion against atherosclerosis and ischemia/reperfusion injury. In this review, we summarize the most recent litera-ture investigating the effects of HDL-S1P on cardiovascular health and highlight potential opportunities for clinical translation of these findings.     

A prospective evaluation of apolipoprotein M gene T-778C polymorphism in relation to coronary artery disease in Han Chinese

OBJECTIVES: Apolipoprotein M (apoM) is important for the formation of pre-beta-high-density lipoprotein (HDL) and cholesterol efflux in macrophages. It is demonstrated that single-nucleotide polymorphism (SNP) T-778C of apoM gene is related to type 2 diabetes in Han Chinese. In the present study, we investigated the possible association of apoM polymorphism in relation to coronary artery disease (CAD) in Han Chinese. DESIGN AND METHODS: This case-controlled study consisted of 118 CAD patients who were diagnosed angiographically to have at least 30% stenosis, and 255 unrelated subjects who were used as control. ApoM gene polymorphism in the proximal promoter region was analyzed by PCR-RFLP and serum lipid levels were also measured. RESULTS: It is indicated that CAD patients had increased frequency of C allele on apoM T-778C compared to the controls (14.8% vs. 6.9%, P=0.0008). Multivariable logistic regression analysis indicated that odds ratios (ORs) for all subjects with apoM CC+CT genotypes and C allele were 1.9 (95% CI=1.1-2.9, P<0.0001) and 1.9 (95% CI=1.3-3.2, P<0.0001), respectively. The plasma total cholesterol (TC) levels were significantly higher in individuals with CC or CT genotype than those with TT genotype in both CAD patients and controls. CONCLUSIONS: The present findings suggest that the C allele at nucleotide -778 in the apoM gene is a risk factor for genetic susceptibility to CAD and is also associated with TC levels in Han Chinese.     

消木丹颗粒对非酒精性脂肪肝大鼠FXR、ApoM表达的影响

目的 探讨消木丹颗粒对非酒精性脂肪肝（NAFLD）模型大鼠的治疗作用，并探讨其对FXR/ApoM表达的影响。方法 60只SD大鼠按体质量分为正常组，模型组，消木丹颗粒低、中、高剂量组，多烯磷脂酰胆碱组，除正常组外，其余50只采用高脂膳食喂养12周建立NAFLD大鼠模型，造模成功后灌胃给予相应药物，给药4周后取血清及肝脏组织样本。称取大鼠体质量及肝湿质量，计算肝脏指数；HE染色、油红O染色观察肝脏病理变化；ELISA法检测血脂及肝功能水平；免疫组化观察肝组织FXR、ApoM的表达；qPCR法检测肝组织FXR、ApoM mRNA表达水平，Western blot法检测肝脏上述各项基因的蛋白表达。结果 与模型组比较，消木丹颗粒干预后能显著改善NAFLD大鼠体质量、肝脏指数，降低血清ALT、AST、TC、TG、LDL-C含量，增高HDL-C含量，同时能增强肝脏FXR、ApoM的表达，差异有统计学意义（P<0.05~0.01）。结论 消木丹颗粒可调节NAFLD大鼠肝脏的脂质代谢，改善脂质沉积，其机制可能与调控FXR及其相关基因ApoM有关。      

瘦素与动脉粥样硬化的相关性研究现状

瘦素是近年来研究较多的蛋白质激素,与多种影响动脉粥样硬化的因子有着密切的关系,瘦素可降低动脉保护因子载脂蛋白M和脂联素水平,也可以诱导或者加剧致动脉粥样硬化(Atherosclerosis,AS)因子的表达,且瘦素本身也有促AS的作用,在AS的发生发展中起着重要的作用。     

人载脂蛋白M的表达与纯化

目的:表达人细胞外全长结构域重组人载脂蛋白M(apolipoprotein M,ApoM)并将其纯化.方法:利用人类肝脏cDNA文库做模板,聚合酶链反应(PCR)法扩增ApoM DNA,将测序正确的目的基因片段插入质粒pGEXT相应住点,插入E.coli JM109,转化E.coli DL21(DE3),IPTG诱导蛋白表达.结果:PCR扩增产物经琼脂糖凝胶电泳证实在SDS-PAGE上出现一条560bp的基因片段.测序结果与GenBank公布的人ApoM基因序列完全一致.ApoM cDNA基因片段经IPTG诱导表达重组蛋白,SDS-PAGE电泳分析表明在相对分子量24 kD左右出现新的蛋白条带.结论:成功克隆出人ApoM基因,重组表达出ApoM蛋白.