机构：[1]Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.[2]Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.[3]Department of Neurosurgery and Interventional Neuroradiology, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, National Center for Neurological Disorders, Beijing神经科系统医技科室神经外科放射科首都医科大学宣武医院[4]Department of General Surgery, Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology[5]Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China[6]State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, China[7]State Key Laboratory of Complex, Severe, and Rare Diseases, Beijing, China
IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet-induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs.Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 KO mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies.Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls.Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.
基金：
National Natural Science Foundation of China grant No. 82270403 (to H. Zhao); The National Key Research and Development Program of China grant Nos. 2019YFA0801804 and 2019YFA0801703 (to J. Wang); the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences grant No. 2021-I2M-1-016.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类|1 区医学
小类|2 区血液学2 区外周血管病
最新[2023]版：
大类|1 区医学
小类|2 区血液学2 区外周血管病
第一作者：
第一作者机构：[1]Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.[4]Department of General Surgery, Department of Gastrointestinal Surgery, Beijing Hospital, National Center of Gerontology[5]Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China[6]State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, China[7]State Key Laboratory of Complex, Severe, and Rare Diseases, Beijing, China
推荐引用方式(GB/T 7714)：
Yang Hongqin,Chen Junye,Liu Siyang,et al.Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice[J].Arteriosclerosis, Thrombosis, And Vascular Biology.2024,doi:10.1161/ATVBAHA.123.319756.
APA：
Yang Hongqin,Chen Junye,Liu Siyang,Xue Yunfei,Li Zhiwei...&Zhao Hongmei.(2024).Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice.Arteriosclerosis, Thrombosis, And Vascular Biology,,
MLA：
Yang Hongqin,et al."Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice".Arteriosclerosis, Thrombosis, And Vascular Biology .(2024)
医学