title: Oxidized low-density lipoprotein-induced foam cell formation is mediated by formyl peptide receptor 2.
abstract: The increased level of LDL and its modification into oxLDL has been regarded as an important risk factor for the development of cardiovascular diseases such as atherosclerosis. Although some scavenger receptors including CD36 and RAGE have been considered as target receptors for oxLDL, involvement of other receptors should be investigated for oxLDL-induced pathological responses. In this study, we found that oxLDL-induced foam cell formation was inhibited by formyl peptide receptor 2 (FPR2) antagonist WRW(4). oxLDL also stimulated calcium signaling and chemotactic migration in FPR2-expressing RBL-2H3 cells but not in vector-expressing RBL-2H3 cells. Moreover, oxLDL stimulated TNF-α production, which was also almost completely inhibited by FPR2 antagonist. Our findings therefore suggest that oxLDL stimulates macrophages, resulting in chemotactic migration, TNF-α production, and foam cell formation via FPR2 signaling, and thus likely contributes to atherogenesis.
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714, Republic of Korea.
authors.forename: Ha Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Eunseo
authors.initials: E
authors.lastname: Oh
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Sang Doo
authors.initials: SD
authors.lastname: Kim
authors.affiliation: UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan 689-798, Republic of Korea.
authors.forename: Jeong Kon
authors.initials: JK
authors.lastname: Seo
authors.affiliation: Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714, Republic of Korea; Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710, Republic of Korea. Electronic address: yoesik@skku.edu.
authors.forename: Yoe-Sik
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects; D005487:Foam Cells; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D051381:Rats; D044042:Receptors, Formyl Peptide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008077:Lipoproteins, LDL; D044042:Receptors, Formyl Peptide; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D002118:Calcium
keywords: Atherosclerosis; Foam cell; Formyl peptide receptor 2; Oxidized LDL