Macrophages play a unique role in the plaque calcification by enhancing the osteogenic signals exerted by vascular smooth muscle cells

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• 作者：Koji Ikeda ; Yuka Souma ; Yoshiki Akakabe ; Youhei Kitamura ; Kiyonari Matsuo ; Yoshiaki Shimoda ; Tomomi Ueyama ; Satoaki Matoba ; Hiroyuki Yamada ; Mitsuhiko Okigaki ; Hiroaki Matsubara
• 关键词：Vascular calcification ; Plaque calcification ; Vascular smooth muscle cells ; Macrophages ; Bone morphogenetic protein-2 ; Matrix Gla protein
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：17 August, 2012
• 年：2012
• 卷：425
• 期：1
• 页码：39-44
• 全文大小：317 K

文摘

Vascular calcification is a major risk factor for the cardiovascular disease, yet its underlying molecular mechanisms remain to be elucidated. Recently, we identified that osteogenic signals via bone morphogenetic protein (BMP)-2 exerted by vascular smooth muscle cells (VSMCs) play a crucial role in the formation of atherosclerotic plaque calcification. Here we report a synergistic interaction between macrophages and VSMCs with respect to plaque calcification. Treatment with conditioned medium (CM) of macrophages dramatically enhanced BMP-2 expression in VSMCs, while it substantially reduced the expression of matrix Gla-protein (MGP) that inhibits the BMP-2 osteogenic signaling. As a result, macrophages significantly accelerated the osteoblastic differentiation of C2C12 cells induced by VSMC-CM. In contrast, macrophage-CM did not enhance the osteoblastic gene expressions in VSMCs, indicating that macrophages unlikely induced the osteoblastic trans-differentiation of VSMCs. We then examined the effect of recombinant TNF-¦Á and IL-1¦Â on the VSMC-derived osteogenic signals. Similar to the macrophage-CM, both cytokines enhanced BMP-2 expression and reduced MGP expression in VSMCs. Nevertheless, only the neutralization of TNF-¦Á but not IL-1¦Â attenuated the effect of macrophage-CM on the expression of these genes in VSMCs, due to the very low concentration of IL-1¦Â in the macrophage-CM. On the other hand, VSMCs significantly enhanced IL-1¦Â expression in macrophages, which might in turn accelerate the VSMC-mediated osteogenic signals. Together, we identified a unique role of macrophages in the formation of plaque calcification in coordination with VSMCs. This interaction between macrophages and VSMCs is a potential therapeutic target to treat and prevent the atherosclerotic plaque calcification.