Division of Cardiology, Foundation for Medical Research, Department of Medicine Specialized Medicine, Faculty of Medicine, University of Geneva, Av. de la Roseraie 64, CH-1211, Geneva 4, Switzerland.
Ospedale Policlinico San Martino Genoa - Italian Cardiovascular Network, 10 Largo Benzi, Genoa, 16132, Italy.
Sci Rep. 2020 Apr 1;10(1):5791. doi: 10.1038/s41598-020-62596-6.
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 Apoect-1 mice. Apoe C57Bl/6 or Apoect-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. Apoect-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.
心营养素-1（CT-1）与心血管（CV）疾病相关。我们研究了 CT-1 缺乏对载脂蛋白 E 敲除 Apoect-1 小鼠动脉粥样硬化发生和进展的影响。apoE C57Bl/6 或 apoect-1 C57Bl/6 小鼠给予正常饮食（NCD）或高胆固醇饮食（HCD）。处死动物后，检测血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇（LDL-C）、游离脂肪酸和系统旁分泌因子。测量主动脉斑块内脂质和胶原含量。采用流式细胞术分析脾、淋巴结和主动脉中的免疫细胞群。与 apoE 小鼠相比，加速动脉粥样硬化的 apoect-1 小鼠总胆固醇、LDL-C、主动脉根部和腹主动脉粥样硬化斑块大小减少，斑块稳定性改善。apoE 小鼠在（HCD）上的 CT-1 缺乏促进了抗炎性免疫细胞反应，表现为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）和保护性 IgM 抗体的增加。晚期动脉粥样硬化中 CT-1 缺乏介导旁分泌因子的调节，如白细胞介素（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 缺乏诱导抗炎和抗动脉粥样硬化作用，从而阻断动脉粥样硬化进展。
