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Autophagy reduces aortic calcification in diabetic mice by reducing matrix vesicle body-mediated IL-1β release

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机构: [1]Department of General Surgery (Vascular Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China [2]Department of Interventional Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China [3]Laboratory of Nucleic Acids in Medicine for National High-Level Talents, Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou, 646000, China [4]Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China [5]Cardiovascular and Metabolic Diseases Key Laboratory of Sichuan, Luzhou, 646000, China [6]Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China [7]Department of Gastroenterology, Clinical Medical College and the First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, 610500, China [8]Department of Vascular and Interventional, Chongqing University Cancer Hospital, Chongqing, 400030, China [9]State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion of Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China
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关键词: Type 2 diabetes mellitus Vascular calcification Matrix vesicle bodies Interleukin-1β

摘要:
Vascular calcification (VC) is a common pathological process of cardiovascular disease that occurs in patients with type 2 diabetes mellitus (T2DM). However, the molecular basis of VC progression remains unknown. A GEO dataset (GSE146638) was analyzed to show that microbodies and IL-1β may play important roles in the pathophysiology of VC. The release of matrix vesicle bodies (MVBs) and IL-1β and the colocalization of IL-1β with MVBs or autophagosomes were studied by immunofluorescence in an in vivo diabetes mouse model with aortic calcification and an in vitro high glucose cell calcification model. MVB numbers, IL-1β levels and autophagy were increased in calcified mouse aortas and calcified vascular smooth muscle cells (VSMCs). IL-1β colocalized with MVBs and autophagosomes. The MVBs from calcified VSMCs induced the calcification of normal recipient VSMCs, and this effect was alleviated by silencing IL-1β. The autophagy inducer rapamycin reduced IL-1β expression and calcification in VSMCs, while these processes were induced by the autophagy inhibitor chloroquine. In conclusion, our results suggested that MVBs could carry IL-1β out of cells and induce VC in normal VSMCs, and these processes could be counteracted by autophagy. These results suggested that MVB-mediated IL-1β release may be an effective target for treating vascular calcification.Copyright © 2023 Elsevier Inc. All rights reserved.

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出版当年[2023]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学 4 区 肿瘤学
最新[2023]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学 4 区 肿瘤学
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出版当年[2023]版:
Q2 ONCOLOGY Q3 CELL BIOLOGY
最新[2023]版:
Q2 ONCOLOGY Q3 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

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第一作者机构: [1]Department of General Surgery (Vascular Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China [2]Department of Interventional Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China [3]Laboratory of Nucleic Acids in Medicine for National High-Level Talents, Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou, 646000, China [4]Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China [5]Cardiovascular and Metabolic Diseases Key Laboratory of Sichuan, Luzhou, 646000, China
通讯作者:
通讯机构: [1]Department of General Surgery (Vascular Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China [2]Department of Interventional Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China [3]Laboratory of Nucleic Acids in Medicine for National High-Level Talents, Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou, 646000, China [4]Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China [5]Cardiovascular and Metabolic Diseases Key Laboratory of Sichuan, Luzhou, 646000, China
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