Beraprost Attenuates Starvation‐Induced Apoptosis and Protects Feline Endothelial Cells

Abstract

OBJECTIVES: This study aimed to establish an in vitro model of feline endothelial cells (FECs) undergoing apoptosis when cultured under various nutrient deprivation (starvation) conditions to investigate the protective effects of beraprost and its stereoisomers on endothelial cells. METHODS: Various starvation conditions were tested to induce apoptosis in immortalized feline aortic endothelial cells as assessed by measuring caspase-3/7 activity. The anti-apoptotic effects of the racemic mixture of beraprost and the stereoisomers beraprost-314d and beraprost-315d contained in the racemic mixture were determined by measuring caspase-3/7 activity and Bax/Bcl2 gene expression and performing the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Starvation significantly increased caspase-3/7 activity and induced apoptosis in FECs. Beraprost and beraprost-314d efficiently inhibited caspase-3/7 activation in a dose-dependent manner, whereas beraprost-315d exhibited lower potency. Beraprost downregulated Bax expression and reduced the number of TUNEL-positive cells, confirming its anti-apoptotic effects. CONCLUSION AND RELEVANCE: Beraprost effectively attenuates starvation-induced apoptosis-associated events in cultured immortalized feline aortic endothelial cells, inhibits caspase-3/7 activity, and modulates Bax expression. These findings suggest a potential hypothesized mechanism that may contribute to the clinical efficacy of beraprost observed in feline CKD, although further validation using renal endothelial cells and in vivo models is required.