Electronegative LDL Promotes Inflammation and Triglyceride Accumulation in Macrophages

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 3; p. 583
• Main Authors: Puig, Núria, Montolio, Lara, Camps-Renom, Pol, Navarra, Laia, Jiménez-Altayó, Francesc, Jiménez-Xarrié, Elena, Sánchez-Quesada, Jose Luis, Benitez, Sonia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2020; MDPI
• Subjects: Apoptosis; Atherosclerosis; Cardiovascular disease; CD14 antigen; CD36 antigen; Cell differentiation; Cytokines; electronegative ldl; Endothelial cells; Flow cytometry; foam cells; Gene expression; Granulocytes; hdl; High density lipoprotein; Humans; Inflammation; Inflammation - chemically induced; lipid droplets; Lipids; Lipoproteins; Lipoproteins, LDL - adverse effects; Low density lipoprotein; LOX-1 protein; Macrophages; Macrophages - immunology; Monocytes; Scavenger receptors; Thin-layer chromatography; tlr4; TLR4 protein; Toll-like receptors; triglycerides; Triglycerides - adverse effects; United States > US; foam cells; HDL; macrophages; inflammation; electronegative LDL; triglycerides; lipid droplets; TLR4; scavenger receptors
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9030583

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.