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富含胆固醇乳剂在有或无冠状动脉疾病受试者中的血浆动力学

Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease.

作者信息

Santos Raul D, Hueb Whady, Oliveira Antonio A, Ramires Jose A F, Maranhão Raul C

机构信息

Lipid Metabolism Laboratory, the Heart Institute (INCOR), Medical School Hospital (InCor-HCFMUSP), University of São Paulo, São Paulo, Brazil.

出版信息

J Lipid Res. 2003 Mar;44(3):464-9. doi: 10.1194/jlr.M200331-JLR200. Epub 2002 Dec 1.

Abstract

A cholesterol-rich emulsion (LDE) that resembles the LDL lipidic structure is taken-up by LDL receptors after intravenous injection by means of apolipoprotein E it acquires in the circulation and can be used to probe LDL metabolism. In this study, LDE was labeled with [14C]cholesteryl oleate and [3H]cholesterol and injected into 19 patients with coronary artery disease (CAD) and into 14 subjects without CAD to verify whether the kinetic behavior of the radioactive lipids is different in CAD. Blood was sampled over 24 h for radioactivity measurement after lipid extraction and separation by thin-layer chromatography. Fractional clearance rate (FCR, in h-1) of [14C]cholesteryl ester was not different in CAD and nonCAD expressed as median (25%; 75%): 0.08 (0.062; 0.134) h-1 versus 0.06 (0.04; 0.083) h-1, P = 0.167. However, [3H]cholesterol FCR was greater in CAD than in nonCAD (mean +/- SEM): 0.163 +/- 0.016 h-1 versus 0.077 +/- 0.014 h-1, P < 0.001. Esterification of the LDE [3H]cholesterol was also greater in CAD subjects than nonCAD at 10 h and 24 h after emulsion injection (P = 0.029 and 0.024 respectively). In conclusion, both removal from the plasma and esterification of the LDE-cholesterol were increased in CAD. These findings may contribute for unraveling pro-atherogenic mechanisms and the establishment of novel CAD markers.

摘要

一种类似于低密度脂蛋白(LDL)脂质结构的富含胆固醇的乳剂(LDE),在静脉注射后,通过其在循环中获得的载脂蛋白E被LDL受体摄取,可用于探究LDL代谢。在本研究中,LDE用[14C]胆固醇油酸酯和[3H]胆固醇标记,并注入19例冠心病(CAD)患者和14例无CAD的受试者体内,以验证CAD患者中放射性脂质的动力学行为是否不同。脂质提取并经薄层色谱分离后,在24小时内采集血样进行放射性测量。以中位数(25%;75%)表示,CAD组和非CAD组中[14C]胆固醇酯的分数清除率(FCR,单位:h-1)无差异:分别为0.08(0.062;0.134)h-1和0.06(0.04;0.083)h-1,P = 0.167。然而,CAD组中[3H]胆固醇的FCR高于非CAD组(平均值±标准误):分别为0.163±0.016 h- and 0.077±0.014 h-1,P < 0.001。在乳剂注射后10小时和24小时,CAD受试者中LDE [3H]胆固醇的酯化程度也高于非CAD受试者(P分别为0.029和0.024)。总之,CAD患者中LDE-胆固醇从血浆中的清除和酯化均增加。这些发现可能有助于阐明促动脉粥样硬化机制和建立新的CAD标志物。

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