Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism

Area of Science:

• Cardiovascular toxicology
• Cellular and molecular biology
• Environmental health

Background:

• Cardiovascular diseases (CVDs) are a leading cause of mortality.
• Emerging evidence suggests fluoride as a novel risk factor for CVDs.
• The specific mechanisms of fluoride toxicity on vascular smooth muscle cells (VSMCs) are not well understood.

Purpose of the Study:

• To investigate the toxicological effects of fluoride on VSMCs.
• To elucidate the molecular and metabolic pathways affected by fluoride exposure in VSMCs.
• To assess fluoride's role as a CVD risk factor.

Main Methods:

• Establishment of a fluorosis model in Sprague-Dawley rats and A7R5 aortic smooth muscle cell lines.
• In vitro exposure of A7R5 cells to varying fluoride concentrations (0–1200 μmol/L).
• Assessment of cell proliferation, migration, metabolomic profiles, gene expression, and pathway analysis.

Main Results:

• Fluoride exposure impaired VSMCs, aggravating aortic damage in vivo.
• Fluoride inhibited VSMC proliferation and migration in a dose-dependent manner.
• Metabolomic analysis revealed decreased organic acids and lipids; gene network analysis indicated interference with amino acid metabolism and the tricarboxylic acid (TCA) cycle.
• Upregulation of osteopontin (OPN) and α-smooth muscle actin (α-SMA) and downregulation of ABCC1 and BEST1 mRNA levels were observed.

Conclusions:

• Fluoride significantly impairs VSMCs, contributing to cardiovascular pathology.
• Fluoride disrupts critical metabolic pathways, including amino acid metabolism and the TCA cycle, within VSMCs.
• The ATP-binding cassette (ABC) transporters pathway is implicated in fluoride-induced VSMC dysfunction, highlighting fluoride as an emerging CVD risk factor.