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Updated: Mar 13, 2026
Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
Endophilin-A2-mediated increase in scavenger receptor expression contributes to macrophage-derived foam cell
Er-Wen Huang1, Can-Zhao Liu2, Si-Jia Liang2
1Cardiac and Cerebral Vascular Research Center, Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Background And Aims:
Macrophage-derived foam cell formation (MFCF) is a crucial step in the pathogenesis of atherosclerosis. Uptake of oxidized low-density lipoprotein (oxLDL) by scavenger receptors is indispensable for MFCF. Endophilin-A2 has been reported to regulate clathrin-mediated endocytosis (CME). In this study, we tested the hypothesis that endophilin-A2 regulates oxLDL uptake and MFCF by mediating CME of oxLDL-scavenger receptor complexes.
Methods:
In vitro MFCF was induced by oxLDL treatment. Involvement of endophilin-A2 in oxLDL cytomembrane binding, cellular uptake, and MFCF was evaluated by manipulation of endophilin-A2.
Results:
Endophilin-A2 was involved in MFCF via scavenger receptor CD36 and scavenger receptor-A (SR-A)-mediated positive feedback pathways. We observed that oxLDL triggered interaction of endophilin-A2 with CD36 or SR-A, and induced an endophilin-A2-dependent activation of the apoptosis signal-regulating kinase-1 (ASK1)/Jun N-terminal kinase (JNK)/p38 signaling pathway. The activation of ASK1-JNK/p38 signal increased expression of both CD36 and SR-A, which promoted oxLDL cytomembrane binding, cellular uptake, and MFCF. In the absence of oxLDL, endophilin-A2 up-regulated the expression of receptors and Dil-oxLDL binding and uptake, but not the intracellular accumulation of lipids. In the presence of oxLDL, the CME inhibitors pitstop2 and ikarugamycin mimicked the inhibiting effect of endophilin-A2 knockdown and eliminated the elevating effect of endophilin-A2 overexpression on oxLDL uptake and MFCF.
Conclusions:
Endophilin-A2 was identified as a novel molecule regulating MFCF by mechanisms attributable to CME and beyond CME.
