Selenium suppressed hydrogen peroxide‐induced vascular smooth muscle cells calcification through inhibiting oxidative stress and ERK activation

Abstract

Atherosclerosis is frequently associated with vascular calcification. Increasing evidences underline that the essential micronutrient selenium may prevent atherosclerosis, but the role of selenium in vascular calcification remains unknown. In this study, we assessed the effect of sodium selenite (Na(2)SeO(3)) on H(2)O(2)-enhanced vascular smooth muscle cells (VSMCs) calcification and examined the involvement of extracellular signal-regulated kinase (ERK) signaling pathway. Hydrogen peroxide enhanced vascular calcification by inducing osteoblastic differentiation of VSMCs, as showed by up-regulating the mRNA expression of type I collagen, osteocalcin, and Runx2, a key transcription factor for osteoblastic differentiation, increasing alkaline phosphatase activity, and calcium deposition. These effects of H(2)O(2) were suppressed by pretreatment of the cells with selenite (0.1-1 µM) for 24 h. In addition, H(2)O(2) activated the phosphorylation of ERK1/2 and inhibition of H(2)O(2)-activated ERK signaling by MEK inhibitor PD98059 blocked the effect of H(2)O(2) on osteoblastic differentiation of VSMCs. Furthermore, H(2)O(2) induced oxidative stress in calcifying VSMCs, as evidenced by the increase of intracellular reactive oxygen species production and malondialdehyde level, and the decrease of total protein thiols content and the activity of antioxidant selenoenzyme glutathione peroxidases. Selenite pretreatment also attenuated H(2)O(2)-induced oxidative stress and ERK activation. These results suggested that selenite suppressed H(2)O(2)-enhanced osteoblastic differentiation and calcification of VSMCs through inhibiting oxidative stress and ERK activation, indicating a potential preventive role for selenium in vascular calcification.