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Palmitate promotes the paracrine effects of macrophages on vascular smooth muscle cells: the role of bone morphogenetic proteins

Authors
 Ji Hyung Chung  ;  Hyun Ju Jeon  ;  Sung-Yu Hong  ;  Da Lyung Lee  ;  Kyung Hye Lee  ;  Soo Hyuk Kim  ;  Ye Sun Han  ;  Ichiro Manabe  ;  Yury I. Miller  ;  Sang-Hak Lee 
Citation
 PLOS ONE, Vol.7(2) : e29100, 2012 
Journal Title
 PLOS ONE 
Issue Date
2012
MeSH
Animals ; Bone Morphogenetic Protein 2/metabolism* ; Bone Morphogenetic Protein 4/metabolism* ; Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Culture Media, Conditioned/pharmacology ; Humans ; Macrophage Activation/drug effects ; Macrophages/cytology* ; Macrophages/drug effects ; Macrophages/metabolism ; Mice ; Muscle, Smooth, Vascular/cytology* ; Myocytes, Smooth Muscle/cytology* ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Neutralization Tests ; Palmitates/pharmacology* ; Paracrine Communication/drug effects* ; Phenotype ; Rats ; Recombinant Proteins/pharmacology
Keywords
Animals ; Bone Morphogenetic Protein 2/metabolism* ; Bone Morphogenetic Protein 4/metabolism* ; Cell Line ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Culture Media, Conditioned/pharmacology ; Humans ; Macrophage Activation/drug effects ; Macrophages/cytology* ; Macrophages/drug effects ; Macrophages/metabolism ; Mice ; Muscle, Smooth, Vascular/cytology* ; Myocytes, Smooth Muscle/cytology* ; Myocytes, Smooth Muscle/drug effects ; Myocytes, Smooth Muscle/metabolism ; Neutralization Tests ; Palmitates/pharmacology* ; Paracrine Communication/drug effects* ; Phenotype ; Rats ; Recombinant Proteins/pharmacology
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.
Files in This Item:
T201200551.pdf Download
DOI
22363399
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Cardiovascular Product Evaluation Center (심혈관제품유효성평가센터) > 1. Journal Papers
Yonsei Authors
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Chung, Ji Hyung(정지형)
Hong, Sung Yu(홍성유)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91675
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