Effect of shear force on SIRT4 in LPS-injured human umbilical vein endothelial cells

Damage and inflammation of endothelial cells are important factors in the pathogenesis of atherosclerosis. Shear and NAD-dependent protein sirtuin-4 (SIRT4) might regulate atherosclerosis through endothelial cells. This study will investigate the mechanism of how shear and SIRT4 regulate human umbilical vein endothelial cells (HUVEC) to affect atherosclerosis. HUVEC were isolated, cultured, and treated with 100 ng/mL lipopolysaccharide (LPS) to mimic endothelial cells’ injury and inflammation. Shear stress is generated by using a parallel-plate fluid flow chamber. MTT assay was used to measure the growth of HUVEC. Flow cytometry was used to detect apoptosis of HUVEC. RT-PCR and western blot were used to detect the expression levels of SIRT4. Levels of SIRT4 was also overexpressed or suppressed by liposome transfection, and LPS was administered to detect cell apoptosis. Compared to control group, LPS treatment significantly inhibited the growth of HUVEC (P < 0.05) but promoted the apoptosis of HUVEC (P < 0.05). Shear force (16 dyn/cm2) significantly reduced LPS-induced growth inhibition and apoptosis of HUVEC (P < 0.05). LPS reduced the expression of SIRT4 in a dose-dependent manner, whereas shear force (16 dyn/cm2) increased the expression levels of SIRT4 in HUVEC. Overexpression of SIRT4 inhibited LPS-induced HUVEC apoptosis (P < 0.05), and silence of SIRT4 enhanced LPS-induced apoptosis (P < 0.05). LPS induced HUVEC apoptosis through reduction of SIRT4 and shear force inhibited LPS-induced apoptosis of HUVEC.