Electronegative LDL Promotes Inflammation and Triglyceride Accumulation in Macrophages
Por:
Puig N., Montolio L., Camps-Renom P., Navarra L., Jiménez-Altayó F., Jiménez-Xarrié E., Sánchez-Quesada J.L., Benitez S.
Publicada:
1 ene 2020
Resumen:
Electronegative low-density lipoprotein (LDL) (LDL(-)), a modified LDL that is present in blood and exerts atherogenic effects on endothelial cells and monocytes. This study aimed to determine the action of LDL(-) on monocytes differentiated into macrophages. LDL(-) and in vitro-modified LDLs (oxidized, aggregated, and acetylated) were added to macrophages derived from THP1 monocytes over-expressing CD14 (THP1-CD14). Then, cytokine release, cell differentiation, lipid accumulation, and gene expression were measured by ELISA, flow cytometry, thin-layer chromatography, and real-time PCR, respectively. LDL(-) induced more cytokine release in THP1-CD14 macrophages than other modified LDLs. LDL(-) also promoted morphological changes ascribed to differentiated macrophages. The addition of high-density lipoprotein (HDL) and anti-TLR4 counteracted these effects. LDL(-) was highly internalized by macrophages, and it was the major inductor of intracellular lipid accumulation in triglyceride-enriched lipid droplets. In contrast to inflammation, the addition of anti-TLR4 had no effect on lipid accumulation, thus suggesting an uptake pathway alternative to TLR4. In this regard, LDL(-) upregulated the expression of the scavenger receptors CD36 and LOX-1, as well as several genes involved in triglyceride (TG) accumulation. The importance and novelty of the current study is that LDL(-), a physiologically modified LDL, exerted atherogenic effects in macrophages by promoting differentiation, inflammation, and triglyceride-enriched lipid droplets formation in THP1-CD14 macrophages, probably through different receptors.
Filiaciones:
Puig N.:
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, 08041, Spain
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Building M, Universitat Autònoma de Barcelona (UAB), 08193 Cerdanyola del Vallès, Barcelona, Spain
Montolio L.:
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, 08041, Spain
Camps-Renom P.:
Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, and IIB-Sant Pau, Barcelona, 08041, Spain
Navarra L.:
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, 08041, Spain
Jiménez-Altayó F.:
Departament of Pharmacology. Neuroscience Institute. Faculty of Medicine, UAB, 08193 Cerdanyola del Vallès, Barcelona, Spain
Jiménez-Xarrié E.:
Stroke Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, and IIB-Sant Pau, Barcelona, 08041, Spain
Sánchez-Quesada J.L.:
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, 08041, Spain
CIBER of Diabetes and Metabolic Diseases (CIBERDEM)Madrid 28029, Spain
Benitez S.:
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, 08041, Spain
Green Published, gold, All Open Access, Gold, Green
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