Related Experiment Video
Updated: Jul 15, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Autophagy reduces aortic calcification in diabetic mice by reducing matrix vesicle body-mediated IL-1β release
Xiaolei Sun1, Yang Zheng2, Linzhuo Xie3
1Department of General Surgery (Vascular Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Department of Interventional Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Laboratory of Nucleic Acids in Medicine for National High-Level Talents, Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou, 646000, China; 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; Cardiovascular and Metabolic Diseases Key Laboratory of Sichuan, Luzhou, 646000, China.
Abstract:
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.
Insights
Matrix vesicle bodies (MVBs) carrying IL-1β contribute to vascular calcification in type 2 diabetes. Autophagy can counteract this process, suggesting MVB-mediated IL-1β release as a potential therapeutic target for vascular calcification.
Area of Science:
- Cardiovascular Biology
- Cell Biology
- Diabetes Research
Background:
- Vascular calcification (VC) is a common complication in type 2 diabetes mellitus (T2DM), but its molecular mechanisms are not fully understood.
- Microbodies and IL-1β are implicated in VC pathophysiology.
Purpose of the Study:
- To investigate the role of matrix vesicle bodies (MVBs) and IL-1β in vascular calcification.
- To explore the potential of autophagy in regulating these processes.
Main Methods:
- Analysis of GEO dataset GSE146638.
- Immunofluorescence in vivo (diabetes mouse model) and in vitro (high glucose VSMC model).
- Assessment of MVB numbers, IL-1β levels, and autophagy markers.
Main Results:
- Increased MVB numbers, IL-1β levels, and autophagy in calcified aortas and VSMCs.
- IL-1β colocalized with MVBs and autophagosomes.
- MVBs from calcified VSMCs induced calcification in normal VSMCs, an effect reduced by IL-1β silencing.
- Autophagy modulation (rapamycin or chloroquine) affected IL-1β expression and VSMC calcification.
Conclusions:
- MVBs mediate IL-1β release, promoting VC in normal VSMCs.
- Autophagy counteracts MVB-mediated IL-1β release and VC.
- Targeting MVB-mediated IL-1β release represents a promising strategy for treating vascular calcification.
