Abstract: FR-PO303
Role and Mechanism of Interaction Between Autophagy and Ferroptosis in Regulating Osteogenic Transformation of Vascular Smooth Muscle Cells in Vascular Calcification
Session Information
- Bone and Mineral Metabolism: Basic
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
Authors
- Wang, Li, Department of Nephrology, Sichuan Provincial People’s Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
- Li, Yi, Department of Nephrology, Sichuan Provincial People’s Hospital, Sichuan Clinical Research Center for Kidney Diseases, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
Background
Vascular calcification could cause death in chronic kidney diseases (CKD) patients, however, its pathogenesis is not clear. Osteogenic transformation of vascular smooth muscle cells (VSMCs) is key to vascular calcification in CKD, but its mechanism has not been fully elucidated. Our previous study has found an interaction between autophagy and ferroptosis involving osteogenic transformation of VSMCs in vascular calcification. This study aimed to elucidate the role of interaction between autophagy and ferroptosis in regulating osteogenic transformation of VSMCs.
Methods
We used the 5/6 nephrectomy rat model with a diet of 1.2 % phosphate at 16 weeks. Rat VSMCs were treated with supplemented medium β-glycerophosphate and CaCl2 for 7 days. All experiments were approved by the ethics committee of Sichuan Provincial People’s Hospital (No. 2017. 36). And we measured autophagy and ferroptosis in CKD vascular calcification. Full-length transcriptome sequencing was performed upon rattus abdominal aortic tissues. After bioinformatics analysis with the results of sequencing, we verified the role of interaction between autophagy and ferroptosis in regulating osteogenic transformation of VSMCs in vascular calcification by molecular biology methods.
Results
The oxidative stress effect was enhanced with vascular calcification in CKD, accompanied by ferroptosis and autophagy in VSMCs. Full-length transcriptome sequencing results indicated differential expression that were related to ferroptosis and autophagy pathways significantly enriched, including significantly upregulated expression of Runx2, Atg7 and ATG5, RAB7A, ARNTL, HSP90, LAMP2A and Beclin-1 in VSMC. Protein-protein interaction analysis showed there were interactions among the differentially expressed genes that were related to autophagy and ferroptosis. Multispectral fluorescence imaging showed that the expressions of GPX4 and Sm22α decreased and the expressions of NCOA4, Smarca4 and Runx2 increased in calcified vessels of CKD.
Conclusion
These findings shed light on the role of interaction between autophagy and ferroptosis in regulating CKD-associated vascular calcification. Further studies are needed to explore the precise mechanism of interaction between autophagy and ferroptosis in CKD vascular calcification.