HMG-CoA reductase inhibitors reduce nicotine-induced expression of cellular adhesion molecules in cultured human coronary endothelial cells.

Smoking predisposes to the development of atherosclerosis and of its complications. The mechanisms responsible for these effects are not completely understood. We have investigated whether nicotine might promote a proatherosclerotic state in human coronary endothelial cells (HCAECs), studying the role of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in preventing these phenomena. Real-time PCR showed that nicotine induced a dose-dependent increase in mRNA levels for vascular cellular adhesion molecule-1 (VCAM-1)/intercellular adhesion molecule-1 (ICAM-1). Fluorescent-activated cell sorting analysis showed that nicotine induced expression of functionally active VCAM-1/ICAM-1, since they increased leukocyte adherence to HCAECs. Oxygen free radicals, Rho A and nuclear factor kappaB (NF-kappaB) play a pivotal role in modulating these effects. Indeed, nicotine caused oxygen free radical production as well as activation of Rho A and NF-kappaB pathways, evaluated by malondialdehyde levels, pulldown assay and by electrophoretic mobility shift assay, respectively. Superoxide dimutase, Rho A (Y-27639) and NF-kappaB inhibitors (pyrrolidine dithiocarbamate ammonium, Bay 11-7082) suppressed nicotine effects on CAM expression. HMG-CoA reductase inhibitors prevented these nicotine-mediated effects by inhibiting free radical generation and by modulating activation of Rho A and NF-kappaB pathways. Nicotine promotes CAM expression on HCAECs, shifting them toward a proatherosclerotic state. These effects might explain, at least in part, the deleterious cardiovascular consequences of cigarette smoking. HMG-CoA reductase inhibitors play an important role in preventing these phenomena.

Cirillo P ，Pacileo M ，De Rosa S ，Calabrò P ，Gargiulo A ，Angri V ，Prevete N ，Fiorentino I ，Ucci G ，Sasso L ，Petrillo G ，Musto D'Amore S ，Chiariello M ... -  《-》

Simvastatin modulates TNFalpha-induced adhesion molecules expression in human endothelial cells.

Zapolska-Downar D ，Siennicka A ，Kaczmarczyk M ，Kołodziej B ，Naruszewicz M ... -  《LIFE SCIENCES》

Cholestin (Monascus purpureus rice) inhibits homocysteine-induced reactive oxygen species generation, nuclear factor-kappaB activation, and vascular cell adhesion molecule-1 expression in human aortic endothelial cells.

Lin CP ，Chen YH ，Chen JW ，Leu HB ，Liu TZ ，Liu PL ，Huang SL ... -  《-》

Rac1 and superoxide are required for the expression of cell adhesion molecules induced by tumor necrosis factor-alpha in endothelial cells.

Chen XL ，Zhang Q ，Zhao R ，Ding X ，Tummala PE ，Medford RM ... -  《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》

4-O-methylgallic acid down-regulates endothelial adhesion molecule expression by inhibiting NF-kappaB-DNA-binding activity.

Lee G ，Na HJ ，Namkoong S ，Jeong Kwon H ，Han S ，Ha KS ，Kwon YG ，Lee H ，Kim YM ... -  《EUROPEAN JOURNAL OF PHARMACOLOGY》