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Electronegative LDL Promotes Inflammation and Triglyceride Accumulation in Macrophages Puig Grifol, Núria Montolio, Lara Camps-Renom, Pol Navarra, Laia Jiménez Altayó, Francesc Jiménez Xarrié, Elena Sánchez Quesada, José Luis Benitez, Sonia Universitat Autònoma de Barcelona HDL TLR4 Electronegative LDL Foam cells Inflammation Lipid droplets Macrophages Scavenger receptors Triglycerides Altres ajuts: This research was funded by grants 158/U/2017 from Fundacio La Marato TV3. 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. 2020 Article https://ddd.uab.cat/record/241128 urn:10.3390/cells9030583 urn:oai:ddd.uab.cat:241128 urn:articleid:20734409v9n3ecells9030583 urn:scopus_id:85089547011 urn:pmid:32121518 urn:oai:egreta.uab.cat:publications/1aa69dc7-9db0-4b68-b5d2-8ba23cde193a urn:pmc-uid:7140452 urn:pmcid:PMC7140452 urn:oai:pubmedcentral.nih.gov:7140452 eng Instituto de Salud Carlos III PI16-00471 Instituto de Salud Carlos III CB07-08-0016 Instituto de Salud Carlos III RD16-0019-0010 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1149 Cells ; Vol. 9 Núm. 3 (january 2020) open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/ application/pdf