The Phosphoinositide 3-Kinase Signaling Pathway is Involved in the Control of Modified Low-Density Lipoprotein Uptake by Human Macrophages

被引：13
作者：
Michael, Daryn R. [1 ]
Davies, Thomas S. [1 ]
Laubertova, Lucia [1 ,2 ]
Gallagher, Hayley [1 ]
Ramji, Dipak P. [1 ]
机构：
[1] Cardiff Univ, Cardiff Sch Biosci, Cardiff CF10 3AX, S Glam, Wales
[2] Comenius Univ, Jessenius Fac Med, Inst Med Biochem, Martin 03601, Slovakia
来源：
LIPIDS | 2015年 / 50卷 / 03期
关键词：
Atherosclerosis; Foam cell; Cholesterol; Macrophage; Phosphoinositide; 3-kinase; FOAM CELL-FORMATION; FLUID-PHASE PINOCYTOSIS; SCAVENGER RECEPTOR-A; HYPERLIPIDEMIC MICE; SR-A; ATHEROSCLEROTIC LESIONS; CARDIOVASCULAR-DISEASE; LIPID-METABOLISM; GENE-EXPRESSION; PI3K INHIBITORS;
D O I：
10.1007/s11745-015-3993-0
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The transformation of macrophages into lipid-loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor-mediated uptake of modified LDL, mediated primarily by scavenger receptors-A (SR-A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3-kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR-A, CD36 and LPL was attenuated by LY294002. The use of isoform-selective PI3K inhibitors showed that PI3K-beta, -gamma and -delta were all required for the expression of SR-A and CD36 whereas only PI3K-gamma was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis.
引用
收藏
页码：253 / 260
页数：8
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