Chen Junye, Li Kang, Shao Jiang, Lai Zhichao, Gao Ran, Wang Chaonan, Song Xitao, Guo Wenjun, Yu Xiaoxi, Du Fenghe, Zhu Zhan, Wang Jiaxian, Ma Jiangyu, Xu Leyin, Zhou Yan, Liu Jianghao, Shu Keqiang, Zhao Hongmei, Wang Jing, Liu Bao
Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China.
Front Cardiovasc Med. 2022 Apr 8;9:851603. doi: 10.3389/fcvm.2022.851603. eCollection 2022.
Atherosclerotic disease has become the major cause of death worldwide. Smoking, as a widespread independent risk factor, further strengthens the health burden of atherosclerosis. Irisin is a cytokine that increases after physical activity and shows an atheroprotective effect, while its specific mechanism in the process of atherosclerosis is little known. The reversal effect of irisin on intimal thickening induced by smoking-mediated atherosclerosis was identified in mice through the integrin αVβ5 receptor. Endothelial cells treated with nicotine and irisin were further subjected to RNA-seq for further illustrating the potential mechanism of irisin in atherosclerosis, as well as the wound healing assays, CCK-8 assays, β-gal staining and cell cycle determination to confirm phenotypic alterations. Endothelial differential expressed gene enrichment showed focal adhesion for migration and proliferation, as well as the P53 signaling pathway for cell senescence and cell cycle control. Irisin exerts antagonistic effects on nicotine-mediated migration and proliferation the integrin αVβ5/PI3K pathway. In addition, irisin inhibits nicotine-mediated endothelial senescence and cell cycle arrest in G0/G1 phase P53/P21 pathway. This study further illustrates the molecular mechanism of irisin in atherosclerosis and stresses its potential as an anti-atherosclerotic therapy.
动脉粥样硬化疾病已成为全球主要死因。吸烟作为一种广泛存在的独立危险因素，进一步加重了动脉粥样硬化的健康负担。鸢尾素是一种在体育活动后增加并具有抗动脉粥样硬化作用的细胞因子，但其在动脉粥样硬化过程中的具体机制尚不清楚。通过整合素αVβ5受体在小鼠中确定了鸢尾素对吸烟介导的动脉粥样硬化所致内膜增厚的逆转作用。对用尼古丁和鸢尾素处理的内皮细胞进行RNA测序，以进一步阐明鸢尾素在动脉粥样硬化中的潜在机制，并进行伤口愈合试验、CCK-8试验、β-半乳糖苷酶染色和细胞周期测定以确认表型改变。内皮细胞差异表达基因富集显示与迁移和增殖相关的粘着斑，以及与细胞衰老和细胞周期控制相关的P53信号通路。鸢尾素通过整合素αVβ5/PI3K途径对尼古丁介导的迁移和增殖发挥拮抗作用。此外，鸢尾素通过P53/P21途径抑制尼古丁介导的内皮细胞衰老和细胞周期停滞于G0/G1期。本研究进一步阐明了鸢尾素在动脉粥样硬化中的分子机制，并强调了其作为抗动脉粥样硬化治疗手段的潜力。
