Selenium suppresses oxidative-stress-enhanced vascular smooth muscle cell calcification by inhibiting the activation of the PI3K/AKT and ERK signaling pathways and endoplasmic reticulum stress

Abstract

Vascular calcification is a prominent feature of many diseases, including atherosclerosis, and it has emerged as a powerful predictor of cardiovascular morbidity and mortality. A number of studies have examined the association between selenium and risk of cardiovascular diseases, but little is known about the role of selenium in vascular calcification. To determine the role of selenium in regulating vascular calcification, we assessed the effect of sodium selenite on oxidative-stress-enhanced vascular smooth muscle cell (VSMC) calcification and the underlying mechanism. Oxidative stress induced by xanthine/xanthine oxidase increased apoptosis, as determined by Hoechst 33342 staining and annexin V/propidium iodide staining, and it enhanced osteoblastic differentiation and calcification of VSMCs, on the basis of alkaline phosphatase activity, the expression of Runx2 and type I collagen, and calcium deposition. These effects of oxidative stress were significantly inhibited by selenite. The following processes may explain the inhibitory effects of selenite: (1) selenite significantly suppressed oxidative stress, as evidenced by the decrease of the oxidative status of the cell and lipid peroxidation levels, as well as by the increase of the total protein thiol content and the activity of the antioxidant selenoenzyme glutathione peroxidase; (2) selenite significantly attenuated oxidative-stress-induced activation of the phosphatidylinositol 3-kinase/AKT and extracellular-signal-regulated kinase signaling pathways, resulting in decreased osteoblastic differentiation of VSMCs; (3) selenite significantly inhibited oxidative-stress-activated endoplasmic reticulum stress, thereby leading to decreased apoptosis. Our results suggest a potential role of selenium in the prevention of vascular calcification, which may provide more mechanistic insights into the relationship between selenium and cardiovascular diseases.

Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species

“…S7). It also has been reported that by inhibiting the activation of the PI3K/AKT and ERK signaling pathways and endoplasmic reticulum stress, Se can suppress oxidative-stress-enhanced vascular smooth muscle cell calcification60, further reducing the levels of IL-1β, TNF- α, oxidative stress, and NF- κ B activation61. On the contrary, a diet with a Se deficiency weakens antioxidant capacity62.…”

Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases

“…Furthermore, 7-ketocholesterol-induced ERS caused macrophage apoptosis. ERS also promoted oxidative stress and enhanced calcification of vascular smooth muscle cells [80] .…”

MICS, an easily ignored contributor to arterial calcification in CKD patients

“…Several observational studies that involved hemodialysis patients suggested that lower serum Mg concentration was significantly associated with the presence of AC, while long-term treatment with Mg had a protectable effect on CAC (33,94). In a VSMC calcification model, Liu et al (55) found that selenium significantly suppressed oxidative stress and inhibited AC. However, not all the nutrient inadequacy is associated with AC in CKD (76).…”