Abstract
Hyperglycemia is the main feature of diabetes and may increase the risk of vascular calcification (VC), which is an independent predictor for cardiovascular and cerebrovascular diseases (CCD). Selenium (Se) may decrease the risk of CCD, and previous studies confirmed that Se-containing protein from Se-enriched Spirulina platensis (Se-SP) exhibited novel antioxidant potential. However, the effect of Se-SP against VC has been not investigated. Herein, the protective effect and underlying mechanism of Se-SP against high glucose-induced calcification in mouse aortic vascular smooth muscle cells (MOVAS) were explored. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) results showed time-dependent uptake of Se-SP in MOVAS cells, which significantly inhibited high glucose-induced abnormal proliferation. Se-SP co-treatment also effectively attenuated high glucose-induced calcification of MOVAS cells, followed by decreased activity and expression of alkaline phosphatase (ALP). Further investigation revealed that Se-SP markedly prevented reactive oxygen species (ROS)-mediated DNA damage in glucose-treated MOVAS cells. ROS inhibition by glutathione (GSH) effectively inhibited high glucose-induced calcification, indicating that Se-SP could act as ROS inhibitor to inhibit high glucose-induced DNA damage and calcification. Moreover, Se-SP dramatically attenuated high glucose-induced dysfunction of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathways. Se-SP after Se addition achieved enhanced potential in inhibiting high glucose-induced calcification, which validated that Se-SP as a new Se species could be a highly effective treatment for human CCD.
Highlights
Diabetes is a metabolic disease characterized by high glucose and hyperinsulinemia that has reached epidemic proportions (Ogurtsova et al, 2017)
Chronic hyperglycemia is the main characteristic of diabetes, which can cause vascular inflammation, vasoconstriction, thrombosis, Vascular calcification (VC), and atherosclerosis by stimulating reactive oxygen species (ROS) overproduction and generation of pro-inflammatory cytokines and advanced glycation end products (Paneni et al, 2013; Baktiroglu et al, 2016; Henning, 2018)
Cerebral arterial calcification is associated with the occurrence of stroke (Bugnicourt et al, 2011), cognitive impairment, and dementia (Bos et al, 2015), and a high level of cerebral arterial calcification is emerging as a predictor of poor neurological recovery after revascularization treatment in ischemic stroke patients (Lee et al, 2015)
Summary
Diabetes is a metabolic disease characterized by high glucose and hyperinsulinemia that has reached epidemic proportions (Ogurtsova et al, 2017). The protective effects and mechanism of Se-containing protein from Se-enriched S. platensis (SeSP) against high glucose-induced calcification of MOVAS cells were explored. MOVAS cells from American Type Culture Collection (ATCC, Manassas, VA, United States) were cultured with complete Dulbecco’s minimum essential medium containing 5 mM glucose at 37◦C and 5% CO2. Cells in 6-well culture plates were washed with PBS and subsequently fixed with 10% formaldehyde for 10 min. They were washed with PBS and stained with 0.1% alizarin red for 20 min at room temperature. Total protein samples were prepared and quantified by BCA kits. MOVAS cells seeded in six-well plates were pre-incubated with DCFH-DA for 15 min in dark and treated with 25 mM glucose for 10–120 min. Bars with different signs are statistically significance at the level of P < 0.05
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