system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Atorvastatin, Cell Compartmentation, Chemokine CXCL1, Chemokines, E-Selectin, Endocytosis, Fatty Acids, Monounsaturated, Fluvastatin, Heptanoic Acids, Human Umbilical Vein Endothelial Cells, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Indoles, Interleukin-1beta, Intracellular Space, Multivesicular Bodies, Pravastatin, Prenylation, Pyrroles, Simvastatin, Solubility, Subcellular Fractions, Tetraspanin 30.
user
Do statins affect the presentation of endothelial chemokines by targeting to multivesicular bodies? Context: In addition to lowering cholesterol, statins are thought to beneficially modulate inflammation. Several chemokines including CXCL1/growth-related oncogene (GRO)-α, CXCL8/interleukin (IL)-8 and CCL2/monocyte chemoattractant protein (MCP)-1 are important in the pathogenesis of atherosclerosis and can be influenced by statin-treatment. Recently, we observed that atorvastatin-treatment alters the intracellular content and subcellular distribution of GRO-α in cultured human umbilical vein endothelial cells (HUVECs). The objective of this study was to investigate the mechanisms involved in this phenomenon. The effect of atorvastatin on secretion levels and subcellular distribution of GRO-α, IL-8 and MCP-1 in HUVECs activated by interleukin (IL)-1β were evaluated by ELISA, confocal microscopy and immunoelectron microscopy. Atorvastatin increased the intracellular contents of GRO-α, IL-8, and MCP-1 and induced colocalization with E-selectin in multivesicular bodies. This effect was prevented by adding the isoprenylation substrate GGPP, but not the cholesterol precursor squalene, indicating that atorvastatin exerts these effects by inhibiting isoprenylation rather than depleting the cells of cholesterol.
assistant
Atorvastatin targets inflammatory chemokines to the endocytic pathway and multivesicular bodies and may contribute to explain the anti-inflammatory effect of statins at the level of endothelial cell function. Final Decision: yes