Abstract: TH-PO217
Role of Peroxisomes in CKD-Associated Vascular Calcification
Session Information
- Hypertension and CVD: Basic Research Findings
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- He, Fan, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Zhang, Cailin, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Li, Qing, Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
Background
Vascular calcification is highly prevalent and strongly correlated to all-cause and cardiovascular mortality in CKD patients. Peroxisomes are important organelles that regulate various metabolic processes, such as fatty acid oxidation and phospholipid synthesis, thus play an important role in the maintenance of cellular homeostasis. However, the regulatory role of peroxisomes in vascular calcification has not been elucidated. This study aimed to explore the role of peroxisomes in CKD associated vascular calcification.
Methods
The vascular calcification model of CKD mice was used to collect thoracic aortas for transcriptomics, fee-targeted metabolomics and lipidomics analysis. Knockdown or overexpression of peroxisome biogenesis-related genes or ether-lipid synthesis-related genes in vascular smooth muscle cells were performed to detect changes in the degree of vascular calcification. Western blotting, calcium deposition assay, ARS staining, and Von Kossa staining were used to detect vascular calcification.
Results
Combined with the results of transcriptomic analysis, we found that that the peroxisome pathway and ferroptosis pathway were elevated in response to vascular calcification. Moreover, taking advantage of RNA-seq and in vitro experiments, we found that modulating peroxisome content can modulate vascular calcification via regulating ferroptosis. In addition, lipidomic analysis revealed abnormal lipid metabolism in calcified vessels. By knocking down AGPS, the ether-lipid synthesis gene, vascular calcification can be attenuated by inhibiting ferroptosis.
Conclusion
The present results indicate that peroxisomes may regulate ferroptosis levels and ultimately vascular calcification by regulating ether-lipid synthesis.
Funding
- Government Support – Non-U.S.