AIMS Secreted factors produced by adipose tissue are involved in the pathogenesis of cardiovascular disease. We previously identified adipolin, also known as C1q/TNF-related protein 12, as an insulin-sensitizing adipokine. However, the role of adipolin in vascular disease remains unknown. Here, we investigated whether adipolin modulates pathological vascular remodelling. METHODS AND RESULTS Adipolin-knockout (APL-KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery. APL-KO mice showed increased neointimal thickening after vascular injury compared with WT mice, which was accompanied by an enhanced inflammatory response and vascular cell proliferation in injured arteries. Adipolin deficiency also led to a reduction in transforming growth factor-β (TGF-β) 1 protein levels in injured arteries. Treatment of cultured macrophages with adipolin protein led to a reduction in lipopolysaccharide-stimulated expression of inflammatory mediators, including tumour necrosis factor (TNF)-α, interleukin (IL) 6, and monocyte chemotactic protein (MCP)-1. These effects were reversed by inhibition of TGF-β receptor II (TGF-βRII)/Smad2 signalling. Adipolin also reduced platelet-derived growth factor (PDGF)-BB-stimulated proliferation of vascular smooth muscle cells (VSMCs) through a TGF-βRII/Smad2-dependent pathway. Furthermore, adipolin treatment significantly increased TGF-β1 concentration in media from cultured VSMCs and macrophages. CONCLUSION These data indicate that adipolin protects against the development of pathological vascular remodelling by attenuating macrophage inflammatory responses and VSMC proliferation.

中文翻译：

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Adipolin / CTRP12通过抑制平滑肌细胞生长和巨噬细胞炎症反应，防止病理性血管重塑。

目的脂肪组织产生的分泌因子参与心血管疾病的发病机理。我们先前将adipolin（也称为C1q / TNF相关蛋白12）鉴定为胰岛素敏感性adipokine。然而，脂肪脂蛋白在血管疾病中的作用仍是未知的。在这里，我们调查了阿迪泊林是否调节病理性血管重塑。方法和结果将Adipolin基因敲除（APL-KO）和野生型（WT）小鼠进行股线引起的股动脉损伤。与野生型小鼠相比，APL-KO小鼠在血管损伤后显示出新内膜增厚，并伴有炎性反应增强和血管损伤。Adipolin缺乏症还导致受伤的动脉中的转化生长因子-β（TGF-β）1蛋白水平降低。用脂肪蛋白处理培养的巨噬细胞可减少脂多糖刺激的炎症介质表达，包括肿瘤坏死因子（TNF）-α，白介素（IL）6和单核细胞趋化蛋白（MCP）-1。这些作用通过抑制TGF-β受体II（TGF-βRII）/ Smad2信号转导而逆转。Adipolin还通过TGF-βRII/ Smad2依赖性途径减少了血小板衍生的生长因子（PDGF）-BB刺激的血管平滑肌细胞（VSMC）增殖。此外，在培养的VSMC和巨噬细胞的培养基中，脂肪脂处理可显着提高TGF-β1的浓度。结论这些数据表明，阿迪普林通过减轻巨噬细胞炎症反应和VSMC增殖来防止病理性血管重塑的发展。