Abstract 1126: Thiamine Derivative Enhances Mitochondrial Function To Reduce Vascular Calcification

Abstract

Introduction/Background: Vascular calcification significantly impacts cardiovascular disease and mortality. It's exacerbated by mitochondrial dysfunction in vascular smooth muscle cells (VSMCs), influenced by factors such as calcium and phosphate. This study examines the role of thiamine derivatives in improving mitochondrial function, potentially reducing vascular calcification. Research Question/Hypothesis: We hypothesize that thiamine derivatives enhance mitochondrial function, thereby attenuating vascular calcification. Goals/Aims: The aim is to assess the efficacy of thiamine derivatives in enhancing mitochondrial integrity and function to mitigate vascular calcification. Methods/Approach: VSMCs were treated in vitro with phosphate and calcium chloride to induce calcification, along with TTFD (Thiamine tetrahydrofurfuryl disulfide) treatment. Similarly, C57BL/6J mice were administered thiamine derivatives in vivo before inducing aortic calcification. Analysis included calcium deposition, apoptosis, and mitochondrial function assessment. Results/Data: TTFD significantly reduced vascular calcium deposition in VSMCs, both in vitro and in vivo. Mitochondrial function improvement was evidenced by increased oxygen consumption rates and JC-1 aggregate levels. Additionally, TTFD mitigated mitochondrial fission by inhibiting Drp1 phosphorylation at serine 616, leading to reduced apoptosis and osteogenic gene expression. Conclusion: Thiamine derivatives, particularly TTFD, demonstrate potential in mitigating vascular calcification through enhanced mitochondrial function and inhibition of mitochondrial fission. These findings highlight the therapeutic potential of thiamine derivatives in treating vascular calcification-related conditions.