Suppression of Apoptosis by Nitric Oxide via Inhibition of Interleukin-1β–converting Enzyme (ICE)-like and Cysteine Protease Protein (CPP)-32–like Proteases

Abstract

Physiological levels of shear stress alter the genetic programm of cultured endothelial cells and are associated with reduced cellular turnover rates and formation of atherosclerotic lesions in vivo. To test the hypothesis that shear stress (15 dynes/cm²) interferes with programmed cell death, apoptosis was induced in human umbilical venous cells (HUVEC) by tumor necrosis factor-α (TNF-α). Apoptosis was quantified by ELISA specific for histone-associated DNA-fragments and confirmed by demonstrating the specific pattern of internucleosomal DNA-fragmentation. TNF-α (300 U/ml) mediated increase of DNA-fragmentation was completely abrogated by shear stress (446 ± 121% versus 57 ± 11%, P G-monomethyl-l-arginine and was completely reproduced by exogenous NO-donors.