Institute of Chemistry and Biology of Membranes and Nano-objects (CBMN), UMR 5248, CNRS, University of Bordeaux, INP, F-33600 Pessac, France.
Institute of Chemistry and Biology of Membranes and Nano-objects (CBMN), UMR 5248, CNRS, University of Bordeaux, INP, F-33600 Pessac, France.
Biochim Biophys Acta Gen Subj. 2019 May;1863(5):830-838. doi: 10.1016/j.bbagen.2019.01.005. Epub 2019 Feb 12.
Atherosclerosis is a lipid disease characterized by accumulation of low density lipoprotein (LDL) in the artery wall. The transport of LDL across the endothelium of coronary artery is an initiating event of atherosclerosis, whose mechanism remains poorly understood. In the last decade, it has been shown that in caveolin-1 (Cav-1) deficient mice, LDL infiltration in aorta wall is decreased and CD36 expression in aortas is down-regulated, leading to regression of atherosclerotic lesions. In the present study, we show that native LDL endocytosis is decreased in endothelial cells deficient in Cav-1 or CD36. We demonstrate that Cav-1 and CD36 interact in caveolae-rich domains by different biochemical approaches. In addition, confocal microscopy reveals some colocalization of Cav-1 with CD36. These findings indicate that caveolae and CD36 are involved in native LDL endocytosis and suggest that CD36 might be a good candidate for the transport of native LDL across the endothelium, an early event in atherosclerosis.
动脉粥样硬化是一种脂质疾病，其特征是低密度脂蛋白（LDL）在动脉壁中的积累。LDL 穿过冠状动脉内皮的转运是动脉粥样硬化的起始事件，其机制仍不清楚。在过去的十年中，已经表明在窖蛋白-1（Cav-1）缺陷小鼠中，主动脉壁中 LDL 的浸润减少，并且主动脉中 CD36 的表达下调，导致动脉粥样硬化病变的消退。在本研究中，我们表明，内皮细胞中 Cav-1 或 CD36 缺陷会导致内源性 LDL 的内吞作用减少。我们通过不同的生化方法证明 Cav-1 和 CD36 在富含小窝的区域相互作用。此外，共聚焦显微镜显示 Cav-1 与 CD36 有一些共定位。这些发现表明小窝和 CD36 参与内源性 LDL 的内吞作用，并表明 CD36 可能是内源性 LDL 穿过内皮转运的良好候选物，这是动脉粥样硬化的早期事件。
