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.
Highlights
Free fatty acid levels are often elevated in obese individuals and patients with metabolic syndrome or diabetes, and predicts cardiovascular events [1]
Our results suggest that palmitatestimulated macrophages are involved in smooth muscle cells (SMCs) proliferation
This study demonstrated that palmitate influences the paracrine effects of macrophages
Summary
Free fatty acid levels are often elevated in obese individuals and patients with metabolic syndrome or diabetes, and predicts cardiovascular events [1]. The mechanisms by which free fatty acids affect vascular diseases such as atherosclerosis are not completely understood, a growing body of evidence suggests that they are involved in the promotion of vascular inflammation. Saturated fatty acids have been reported to activate monocytes/macrophages and induce the production of several inflammatory mediators such as tumor necrosis factor- a (TNF- a), interleukin-6 (IL-6), and interleukin-1b (IL-1b) [2,3,4]. The proliferation and phenotypic changes of vascular smooth muscle cells (SMCs) from a quiescent and contractile to a synthetic form are critical in atherosclerosis. SMCs interact with other vascular cells including endothelial cells, monocytes, and macrophages and these interactions can influence SMC phenotypes. Known factors involved in the modulation of SMC phenotypes include growth factors such as platelet-derived growth factor (PDGF), angiotensin II, interleukins, and mechanical stimulation [5]
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