血管疾病与肠道胆固醇转运和代谢基因表达相关

W. Widdowson, A. McGowan, J. Phelan, G. Boran, J. Reynolds, J. Gibney
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引用次数: 3

摘要

肠道胆固醇代谢在影响餐后脂蛋白浓度方面是重要的,并且可能在血管疾病的发生中起重要作用。目的本研究评估人类肠道胆固醇代谢基因表达、餐后脂质代谢和内皮功能/早期血管疾病之间的关系。设计/患者100例患者接受常规食管-胃-十二指肠镜检查。采用定量逆转录聚合酶链反应测定十二指肠活检组织中尼曼-匹克c1样1蛋白(NPC1L1)、ABC-G5、ABC-G8、ABC-A1、微粒体组织转运蛋白(MTTP)和甾醇调节元件结合蛋白(SREBP)-2的mRNA水平。餐后测量血脂和血糖水平,空腹评估内皮功能,餐后血流介导扩张(FMD)和颈动脉内膜-中膜厚度(IMT)。将受试者分为高于和低于各基因相对表达中位数的组,比较各组结果。结果两组间在人口统计学变量和经典心血管风险方面没有差异。对于所有基因,高表达组餐后甘油三酯曲线下增量面积更大(P < 0.05)。NPC1L1、ABC-G8和SREBP-2表达高的组餐后载脂蛋白B48 (ApoB48)水平较高(P < 0.05)。在所有基因中,高表达组的餐后FMD低于空腹FMD (P < 0.01)。甘油三酯和ApoB48水平与餐后FMD显著相关。MTTP、ABC-A1、SREBP-2表达高的组颈动脉IMT升高(P < 0.05)。结论肠道胆固醇代谢基因表达与餐后甘油三酯升高、肠道载脂蛋白48升高及餐后FMD降低相关。一些基因也与IMT增加有关。这些发现提示肠道胆固醇代谢在早期血管疾病发展中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Vascular Disease Is Associated With the Expression of Genes for Intestinal Cholesterol Transport and Metabolism
Context Intestinal cholesterol metabolism is important in influencing postprandial lipoprotein concentrations, and might be important in the development of vascular disease. Objective This study evaluated associations between expression of intestinal cholesterol metabolism genes, postprandial lipid metabolism, and endothelial function/early vascular disease in human subjects. Design/Patients One hundred patients undergoing routine oesophago-gastro-duodenoscopy were recruited. mRNA levels of Nieman-Pick C1-like 1 protein (NPC1L1), ABC-G5, ABC-G8, ABC-A1, microsomal tissue transport protein (MTTP), and sterol-regulatory element-binding protein (SREBP)-2 were measured in duodenal biopsies using quantitative reverse transcription polymerase chain reaction. Postprandially, serum lipid and glycemic profiles were measured, endothelial function was assessed using fasting, and postprandial flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT). Subjects were divided into those above and below the median value of relative expression of each gene, and results were compared between the groups. Results There were no between-group differences in demographic variables or classical cardiovascular risks. For all genes, the postprandial triglyceride incremental area under the curve was greater (P < 0.05) in the group with greater expression. Postprandial apolipoprotein B48 (ApoB48) levels were greater (P < 0.05) in groups with greater expression of NPC1L1, ABC-G8, and SREBP-2. For all genes, postprandial but not fasting FMD was lower (P < 0.01) in the group with greater expression. Triglyceride and ApoB48 levels correlated significantly with postprandial FMD. Carotid artery IMT was greater (P < 0.05) in groups with greater expression of MTTP, ABC-A1, and SREBP-2. Conclusion Intestinal cholesterol metabolism gene expression is significantly associated with postprandial increment in triglycerides, intestinal ApoB48, and reduced postprandial FMD. Some genes were also associated with increased IMT. These findings suggest a role of intestinal cholesterol metabolism in development of early vascular disease.
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