Cardiovascular Product Evaluation Center, Cardiovascular Research Institute, Yonsei University Health System, Seoul, Korea.
PLoS One. 2012;7(2):e29100. doi: 10.1371/journal.pone.0029100. Epub 2012 Feb 21.
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.
饱和脂肪酸已知能激活巨噬细胞并诱导血管炎症。虽然激活的巨噬细胞中的细胞因子会影响其他血管细胞，但饱和脂肪酸对巨噬细胞旁分泌作用的影响尚未完全了解。在这里，我们研究了棕榈酸对巨噬细胞对血管平滑肌细胞（SMC）及其介质的影响。经棕榈酸盐刺激的 RAW264.7 细胞条件培养基处理后，SMC 增殖显著增加。发现经棕榈酸盐条件培养基处理后 SMC 迁移增加。SM α-肌动蛋白和 SM22α 在经棕榈酸盐条件培养基处理的 SMC 中减少。当 RAW264.7 细胞受到棕榈酸盐刺激时，会向细胞培养基中分泌更多的骨形态发生蛋白（BMP）2 和 BMP4。用中和抗 BMP 抗体或用 siRNA 敲低 BMP 处理后，SMC 增殖、迁移和表型变化减弱。这些蛋白质的影响通过直接用重组 BMP2 和 BMP4 处理 SMC 进一步得到证实。特别是，BMPs 对 SMC 迁移和表型变化的影响明显，而对 SMC 增殖的影响似乎不明显或适度。总之，棕榈酸促进了巨噬细胞对 SMC 增殖、迁移和表型变化的旁分泌作用。刺激的巨噬细胞的作用至少部分是由 BMP2 和 BMP4 介导的。这些结果提示了一种新的机制，将饱和脂肪酸与血管疾病的进展联系起来，其可能是由巨噬细胞中的 BMP 介导的。
