Endothelial cell aging and apoptosis in prevention and disease: E-selectin expression and modulation as a model.

Endothelial cell senescence and apoptosis are features of numerous human pathologies including atherosclerosis, allograft vasculopathy, heart failure, diabetic retinopathy and scleroderma. In contrast, endothelial cell activation and replication associated with vessel proliferation and angiogenesis are now therapeutic targets in other diseases such as cancer and macular dystrophy. Finally, preventive medicine, in particular cardiovascular and cancer chemoprevention, commonly involve the endothelium. Here we discuss several aspects of the interplay between endothelial cell aging, apoptosis and senescence. Further, we show novel microarray data on endothelial cells "aged" in culture, and note that many genes regulated by the aging process are also modulated by a chemopreventive anti-angiogenic and anti-apoptotic drug, N-acetyl-cysteine (NAC). Focusing on one of these genes, the leukocyte adhesion protein E-selectin, we show that E-selectin is down-modulated with time in culture and upon treatment with NAC at mRNA and protein levels. This correlates with reduced adhesion of breast cancer cells and NF-kB activation in NAC treated endothelial cells. These data underscore the effects of a chemoprevention agent in modulating parameters associated with endothelial cell aging.