Cardiotrophin-1 (CT-1) is associated with cardiovascular (CV) diseases. We investigated the effect of CT-1 deficiency in the development and progression of atherosclerosis in double knockout Apoe^−/−ct-1^−/− mice. Apoe^−/− C57Bl/6 or Apoe^−/−ct-1^−/− C57Bl/6 mice were fed a normal chow diet (NCD) or a high-cholesterol diet (HCD). After sacrifice, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), free fatty acids and systemic paracrine factors were measured. Intraplaque lipid and collagen content were quantified in the aortic sections. Immune cell populations in spleen, lymph nodes and aorta were analysis by flow cytometry. Apoe^−/−ct-1^−/− mice in accelerated atherosclerosis exhibited a reduction of total cholesterol, LDL-C, atherosclerotic plaques size in the aortic root and in the abdominal aorta and improved plaque stability in comparison to Apoe^−/− mice. CT-1 deficiency in Apoe^−/− mice on (HCD) promoted atheroprotective immune cell responses, as demonstrated by a rise in plasma anti-inflammatory immune cell populations (regulatory T cells, Tregs; regulatory B cells, Bregs and B1a cells) and atheroprotective IgM antibodies. CT-1 deficiency in advanced atherosclerosis mediated regulation of paracrine factors, such as interleukin (IL)-3, IL-6, IL-9, IL-15, IL-27, CXCL5, MCP-3, MIP-1α and MIP-1β. In a model of advanced atherosclerosis, CT-1 deficiency induced anti-inflammatory and atheroprotective effects which resulted in abrogation of atheroprogression.

心肌营养素1（CT-1）与心血管（CV）疾病相关。我们调查了CT-1缺乏对双敲除Apoe ^-/- ct-1 ^-/-小鼠动脉粥样硬化发展和进展的影响。向Apoe ^-/- C57Bl / 6或Apoe ^-/- ct-1 ^-/- C57Bl / 6小鼠喂食正常食物（NCD）或高胆固醇饮食（HCD）。处死后，测量血清甘油三酸酯，总胆固醇，低密度脂蛋白胆固醇（LDL-C），游离脂肪酸和全身性旁分泌因子。在主动脉部分定量斑内脂质和胶原蛋白含量。通过流式细胞术分析脾脏，淋巴结和主动脉中的免疫细胞群。Apoe ^-/- ct-1 ^-/-与Apoe ^-/-小鼠相比，处于加速动脉粥样硬化中的小鼠表现出总胆固醇，LDL-C，主动脉根部和腹主动脉中动脉粥样硬化斑块大小的减少，并改善了斑块稳定性。Apoe中的CT-1缺陷^-/-（HCD）小鼠促进了抗动脉粥样硬化性免疫细胞反应，如血浆抗炎免疫细胞群（调节性T细胞，Tregs；调节性B细胞，Bregs和B1a细胞）和抗动脉粥样硬化IgM抗体的增加所证明。晚期动脉粥样硬化的CT-1缺乏介导旁分泌因子如白介素（IL）-3，IL-6，IL-9，IL-15，IL-27，CXCL5，MCP-3，MIP-1α和MIP- 1β。在晚期动脉粥样硬化模型中，CT-1缺乏会引起抗炎和抗动脉粥样硬化作用，从而导致动脉粥样硬化进展消失。