Research Studies
Study Tracker
Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.
Abstract
Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 ?mol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride’s interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and ?-smooth muscle actin (?-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.
Original abstract online at https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-024-05350-0
Excerpts:
… This study employed in vivo and in vitro experiments investigate the adverse effects of fluoride on VSMCs.
Conclusion
This study marks a groundbreaking achievement in shedding light on the metabolites and metabolic pathways affected by fluoride in VSMCs. For the first time, we have provided a comprehensive report on these impacts and gained a deeper understanding of their implications. Notably, amino acids belonging to the “glutamate family” emerged as highly enriched components across various pathways. This underscores the significance of amino acids metabolism as a central link in fluoride-induced toxicity in VSMCs. Of particular interest is the observation that multiple pathways related to protein synthesis, and interconnected with amino acids metabolism, exhibited significant enrichment. These encompassed pathways such as ABC transporters and aminoacyl-tRNA biosynthesis, among others. While it’s important to acknowledge the study’s limitation in using male rats only and lacking in vivo validation of metabolites, our findings undeniably pave the way for a new direction and an intriguing avenue of exploration in the realm of fluoride toxicity research and fluorosis. In particular, whether ABC transporters is a key link in fluoride induced VSMC cytotoxicity will be the focus of in further research.