Abstract
Abstract Disclosure: S. Kwon: None. M. Kim: None. S. Zerwa: None. S. Kim: None. B. Jueun: None. J. Jeon: None. I. Lee: None. Objectives: Vascular calcification is associated with cardiovascular disease mortality, especially in patients with diabetes mellitus and chronic kidney disease. One of proposed mechanisms for development of vascular calcification suggested mitochondrial dysfunction of vascular smooth muscle cells (VMSCs), especially excessive mitochondrial fission that led to apoptosis and tissue calcium deposit formation. In existing literature, Vitamin B1 inhibited mitochondrial fission and improved mitochondrial function. This study investigated whether inhibiting mitochondrial fission prevents vascular calcification in vitro and in vivo by using inorganic phosphate and cholecalciferol-induced vascular calcification models, respectively. Methods: VMSCs from thoracic aorta of 4-week-old rats were treated by 2.6mM inorganic phosphate and 2mM calcium chloride to induce calcification. 6-week-old male C57BL/6J mice were given vitamin B1 analogue solution or water with daily oral gavage for 13 days, then aortic calcification was induced by subcutaneous injection of 5.5×10-5 IU/kg cholecalciferol for 3 days before sacrifice. Cells and tissues were stained for calcium deposition, (van Kossa stain), apoptosis (TUNEL) and mitochondrial morphology (Mitotracker). Western blotting and quantitative real-time PCR were used to assess calcification pathways and mitochondrial function. Tissue calcium content, normalized with total protein contents, was measured to quantify the extent of calcification. Mitochondrial oxygen consumption ratio (OCR) and mitochondrial membrane potential (JC-1 dye staining) were assessed to analyze quantified mitochondrial function. Results: Calcium deposition in both in vivo and in vitro models were alleviated by vitamin B1 analogue through inhibition of mitochondrial fission and restoration of mitochondrial function. In addition, vitamin B1 analogue downregulated expression of genes related to calcification and osteogenesis, such as bone morphogenic protein 2, osteocalcin, osteopontin, and runt-related transcription factor 2. Conclusion: Prevention of mitochondrial dysfunction in VSMCs may be a viable therapeutic strategy for treatment of vascular calcification. Presentation: Friday, June 16, 2023
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