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Atherosclerosis is a chronic inflammatory disease which initiates by the accumulation of low density lipoprotein (LDL) in the artery wall. Methylseleninic acid (MSA, CH3SeO2H), a metabolite of selenium from animal cells, has exhibited anti-oxidative and anti-cancer activity. However, the effect of MSA on atherosclerosis has not been reported by far. In this study, we investigated the effect of MSA on endothelial integrity.
We used HUVECs to build up cultured endothelial cell monolayers.
MSA treatments at 5 μM could increase the transportation of ox-LDL through monolayers. Immunofluorescence results showed that MSA could disrupt the formation of adherens junction by VE-cadherin. Western blot results further showed that MSA could induce the proteolysis of VE-cadherin in a time-dependent manner. We also found that MSA increased calpain activity by up-regulation of calpain-1 and its membrane localization. Additionally, increase of ox-LDL permeability and proteolysis of VE-cadherin could be attenuated by co-treating with the calpain inhibitor II (ALLM) or calpain inhibitor IV (Z-LLY-FMK).
In conclusion, our results suggest that exogenous MSA promote ox-LDL transport through the leak of cultured endothelial cell monolayers, which caused by the proteolysis of VE-cadherin and the lift of calpain activity.