Impact of LDL-cholesterol exposure on BV-2 microglial cell line

Background: Hypercholesterolemia, a prevalent metabolic condition affecting more than 40% of the global population, is characterized by elevated plasma LDL-cholesterol levels and is a major risk factor for cardiovascular diseases. This condition has been linked to the development of neurodegenerative diseases, and studies have revealed damage to the blood-brain barrier (BBB) and the presence of peripheral elements in the central nervous system (CNS). In response to increased permeability, microglial cells, responsible for maintaining brain homeostasis, can modify their activity and morphology by adapting their responses to protect the other cells. This study aimed to investigate the effects of excess LDL on microglial cells in vitro. Methods: BV-2 line of murine microglial cells was exposed to LDL-cholesterol at concentrations of 50, 100, or 300 μg/mL or PBS (control) for 24 h. Subsequently, a series of assays were conducted to evaluate cell viability, cell density, accumulation of lipid droplets, number of lysosomes, autophagy changes, and receptors involved in LDL endocytosis and inflammatory responses. Results: BV-2 cells exposed to LDL, particularly at the highest concentration, showed accumulation of lipid droplets, which was associated with alterations in the cellular digestion process, such as the increase in lysosomes at the highest concentration, and the decrease in autophagy at both concentrations of LDL. No changes were observed regarding pro-inflammatory cytokines TNFα and IL-1β production after LDL incubation in the cells. Furthermore, incubation with LDL modified the gene expression of the LDL receptor but not of receptors TLR4 and LRP8 associated with the uptake of oxidized or inflammatory LDL. Conclusions: BV-2 cells can endocytosis LDL; however, excess LDL accumulates internally in lipid droplets, which can be associated with cellular dysfunction in vitro.