Aims: Benzo[a]pyrene (BaP), a prominent component of tobacco, has been revealed to induce damage to endothelial progenitor cells (EPCs). Astragaloside IV (AS-IV) is widely used for the treatment of cardiovascular diseases in China. In this study, we evaluated the effects of AS-IV on the function of human EPCs after BaP exposure and explored the underlying mechanism.
Materials and methods: Human umbilical cord blood mononuclear cells were isolated using density gradient centrifugation. Cells of the 4th passage were randomly divided into 6 groups. EPCs of experimental groups were pre-treated with different concentrations (2, 10 and 50 μg/mL) of AS-IV for 2h before exposure to BaP (20 μM) for 24h. The proliferation, migration, and adhesion of the treated EPCs were evaluated using a cell counting kit-8, Transwell assay and adhesion assay respectively. Interleukin-1β, tumor necrosis factor-α, malondialdehyde and SOD contents in the supernatant were evaluated. The expression of RAGE protein was measured by Western blotting.
Key findings: The results demonstrated that AS-IV pre-treatment significantly improved BaP-induced dysfunction of EPCs in terms of proliferation, migration and adhesion. Furthermore, AS-IV reduced the production of reactive oxygen species, malondialdehyde, interleukin-1β and tumor necrosis factor-α of the BaP-treated EPCs. Finally AS-IV pre-treated EPCs showed an increased SOD activity and decreased RAGE protein expression.
Significance: AS-IV is able to prevent BaP-mediated EPC dysfunction by at least inhibiting oxidative stress through the RAGE pathway.
Keywords: Astragaloside IV; Benzo[a]pyrene; Endothelial progenitor cells; RAGE.
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