L32	Pathophysiology of cigarette smoking-induced atherosclerosis.
D.Bernhard, A.Csordas, B.Henderson, A.Rossmann, M.Kind, G.Wick
Innsbruck Biocenter / Innsbruck Medical University, Innsbruck, AT.

Smoking is a significant risk factor for the development of atherosclerosis. However, the pathophysiology of smoking–mediated vessel wall damage is not understood. With tools ranging from analytical chemistry to cell biology, we show that cigarette smoke contains metals that catalyze the direct oxidation of cellular proteins by smoke oxidants. The oxidation of cellular proteins causes a loss of microtubule function, culminating in microtubule depolymerization and proteasome-dependent degradation of α-tubulin. As a consequence of the microtubule collapse, cytoskeletal structures as well as intermediate filaments breakdown, finally leading to a contraction of vascular endothelial cells. In addition, we observed a smoke extract induced release of P-selectin/CD62P, IL-6, and IL-8 from endothelial cells into the supernatant. Increased levels of soluble CD62P and IL-6 are well known to be associated with smoking in humans, and increased permeability of the vascular endothelium is a crucial event in atherogenesis. Further, we were able to show that smoke constituents cause a necrotic, hence pro-inflammatory form of cell death of vascular endothelial cells. This work highlights the compounds and mechanisms via which cigarette smoke induces increased permeability of the vascular endothelium, and defines a mechanism via which smoking contributes to an inflammatory status of the vessel wall.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.