ArticleMolecular medicine (Cambridge, Mass.)2026
IL-6 triggers lysosomal degradation of LDL-R and enhances LDL-C uptake in vascular endothelial cells via macropinocytosis.
Article in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Microplastics and Nanoplastics in Food: Dietary Toxicology Beyond Particle Counts.Comprehensive reviews in food science and food safety · 2026Review
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8 authors.
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Abstract
backgroundEndothelial dysfunction profoundly compromises the barrier function that precludes trans-endothelial entry of low-density lipoprotein cholesterol (LDL-C) into the vessel wall. LDL-C retention in the vessel wall is atherogenic and its flux involves several mechanisms including LDL-receptor (LDL-R) mediated transcytosis, a process that is facilitated by inflammatory stressors. In this study, we aimed to investigate the role of interleukin-6 (IL-6) in regulating LDL-R and LDL-C uptake by vascular endothelial cells.
methodWe used commercially available Human umbilical vein endothelial cells (HUVECs) in this study. Flow cytometry, western blotting, qRT-PCR and ELISA were used to investigate expression of LDL-R and Mylip/IDOL. LDL-C uptake and free cholesterol levels in HUVECs was assessed using flowcytometry and mass-spectrometry respectively.
resultsWe show that HUVECs treated with a combination of IL-6 and soluble IL-6 receptor (sIL-6R) result in a significant reduction in surface expression of LDL-R, an effect that is reversed by soluble gp130Fc – an antagonist of IL-6 trans-singling. Using pharmacological inhibitors and gene silencing techniques, we demonstrate that IL-6 trans-signaling induced downregulation of LDL-R is attained through lysosomal degradation mediated by the E3 ubiquitin ligase Mylip. Conversely, HUVECs treated with IL-6 in combination with sIL-6R exhibit markedly increased uptake of native LDL-C which is also inhibited by sgp130Fc, the actin inhibitor Cytochalasin D and the macropinocytosis inhibitor EIPA. Although stimulation of HUVECs upregulated the expression of scavenger receptors CD36 and CXCL16, their contribution to native LDL-C uptake turned out to be negligible.
conclusionCollectively, this study highlights the role of IL-6 in the regulation of LDL-R expression and cholesterol homeostasis in vascular ECs. IL-6 trans-signaling downregulates LDL-R yet increases LDL-C uptake via an LDL-R–independent, actin-dependent macropinocytosis pathway.
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