Anti-apoptotic effect of activated protein C on lipopolysaccharide-stimulated human umbilical vein endothelial cells is associated with the inhibition of the caspase-3 pathway

Abstract

Activated protein C (APC) is an anticoagulant polypeptide that plays a critical role in coagulation, inflammation and anticoagulation interactions; in addition, it decreases the mortality rate of patients with severe infectious disease. However, the exact mechanisms of these effects remain unclear. The aim of this study was to investigate the effect of APC on human umbilical vein endothelial cell apoptosis upon lipopolysaccharide (LPS) stimulation and to elucidate its underlying mechanisms. Apoptotic changes in cells were determined by examining cell ultra-structure, DNA fragmentation and Annexin V/PI staining. Cell viability and the expression of apoptotic-related factors were measured in LPS-stimulated cells with and without APC treatment. The results showed that the administration of APC decreased the apoptosis of cells by inhibiting the activity of the caspase-3 apoptotic-signaling pathway in LPS-stimulated cells. This study supports the notion that APC treatment may be beneficial for the attenuation of endothelial cell injury caused by severe infectious disease via the regulation of apoptotic pathways. Furthermore, APC may be useful in the treatment of infectious disease.