Ionic silicon improves endothelial cells' survival under toxic oxidative stress by overexpressing angiogenic markers and antioxidant enzymes

Abstract

Oxidative stress, induced by harmful levels of reactive oxygen species, is a common occurrence that impairs proper bone defect vascular healing through the impairment of endothelial cell function. Ionic silicon released from silica-based biomaterials, can upregulate hypoxia-inducible factor-1α (HIF-1α). Yet it is unclear whether ionic Si can restore endothelial cell function under oxidative stress conditions. Therefore, we hypothesized that ionic silicon can help improve human umbilical vein endothelial cells' (HUVECs') survival under toxic oxidative stress. In this study, we evaluated the ionic jsilicon effect on HUVECs viability, proliferation, migration, gene expression, and capillary tube formation under normal conditions and under harmful hydrogen peroxide levels. We demonstrated that 0.5-mM Si⁴⁺ significantly enhanced angiogenesis in HUVECs under normal condition (p < 0.05). HUVECs exposed to 0.5-mM Si⁴⁺ presented a morphological change, even without the bed of Matrigel, and formed significantly more tube-like structures than the control (p < 0.001). In addition, 0.5-mM Si⁴⁺ enhanced cell viability in HUVECs under harmful H₂ O₂ levels. HIF-1α, vascular endothelial growth factor-A, and vascular endothelial growth factor receptor-2 were overexpressed more than twofold in silicon-treated HUVECs, under normal and toxic H₂ O₂ conditions. Moreover, the HUVECs were treated with 0.5-mM Si⁴⁺ overexpressed superoxide dismutase-1 (SOD-1), catalase-1 (Cat-1), and nitric oxide synthase-3 (NOS3) under normal and oxidative stress environment (p < 0.01). A computational model was used for explaining the antioxidant effect of Si⁴⁺ in endothelial cells and human periosteum cells by SOD-1 enhancement. In conclusion, we demonstrated that 0.5-mM Si⁴⁺ can recover the HUVECs' viability under oxidative stress conditions by reducing cell death and upregulating expression of angiogenic and antioxidant factors.

Keywords: angiogenesis; angiogenic markers; antioxidant enzymes; cell survival; endothelial cells; ionic silicon; oxidative stress.