Disruption of vascular endothelial homeostasis by tobacco smoke—impact on atherosclerosis

Abstract

SPECIFIC AIMSBy the year 2020 smoking will be the largest single health problem worldwide. The proatherogenic activity of tobacco smoking is well defined from the medical point of view, but the mechanisms by which smoking contributes to atherosclerosis are largely unknown. Here we set out to examine the effect of cigarette smoking on the vascular endothelium.PRINCIPAL FINDINGS1. Human vascular endothelial cells exposed to tobacco smoke undergo cell death by necrosisFirst we analyzed whether cigarette smoke exerts toxic effects on vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were incubated with aqueous cigarette smoke extracts (TS) for 24 h in order to determine various cell death-associated phenotypes (Fig. 1⤻ ). Upon TS treatment, HUVECs show 1) a necrotic phenotype with the annexin method (Fig. 1a⤻ ), 2) reduced cell viability (Fig. 1b⤻ ), 3) no functional involvement of caspases in TS-mediated cell death (Fig. 1c⤻ ), 4) no caspase-3 activation (Fig. 1d⤻ ), and 5) no PARP ...