title: Palmitate promotes the paracrine effects of macrophages on vascular smooth muscle cells: the role of bone morphogenetic proteins.
abstract: Saturated fatty acids are known to activate macrophages and induce vascular inflammation. Although cytokines from activated macrophage influence other vascular cells, the influence of saturated fatty acids on the paracrine effect of macrophages is not fully understood yet. Here we examined the impact of palmitate on the effect of macrophages on vascular smooth muscle cells (SMCs) and their mediators. SMCs proliferation increased significantly after treatment with conditioned media from palmitate-stimulated RAW264.7 cells. SMC migration was found to be greater after treatment with palmitate-conditioned media. SM α-actin and SM22α were decreased in SMCs treated with palmitate-conditioned media. When stimulated with palmitate, RAW264.7 cells secreted more bone morphogenetic protein (BMP)2 and BMP4 into the cell culture media. SMC proliferation, migration, and phenotypic changes were attenuated after treatment of neutralizing antibodies against BMPs or knockdown of BMPs with siRNA. The influences of these proteins were further confirmed by direct treatment of recombinant BMP2 and BMP4 on SMCs. Particularly, the effects of BMPs on SMC migration on phenotypic change were obvious, whereas their effect on SMC proliferation seemed not significant or modest. In conclusion, palmitate promoted macrophages' paracrine effects on SMC proliferation, migration, and phenotypic change. The effect of stimulated macrophages was mediated, at least in part, by BMP2 and BMP4. These results suggest a novel mechanism linking saturated fatty acids and the progression of vascular diseases that is possibly mediated by BMPs from macrophages.
authors.affiliation: Cardiovascular Product Evaluation Center, Cardiovascular Research Institute, Yonsei University Health System, Seoul, Korea.
authors.forename: Ji Hyung
authors.initials: JH
authors.lastname: Chung
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Jeon
authors.forename: Sung-Yu
authors.initials: SY
authors.lastname: Hong
authors.forename: Da Lyung
authors.initials: DL
authors.lastname: Lee
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Lee
authors.forename: Soo Hyuk
authors.initials: SH
authors.lastname: Kim
authors.forename: Ye Sun
authors.initials: YS
authors.lastname: Han
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.forename: Yury I
authors.initials: YI
authors.lastname: Miller
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009500:Neutralization Tests; D010168:Palmitates / Q000494:pharmacology*; D019899:Paracrine Communication / Q000187:drug effects*; D010641:Phenotype; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D017077:Culture Media, Conditioned; D010168:Palmitates; D011994:Recombinant Proteins