Plasma-induced endothelial activation associated with incident atherosclerosis: prospective results from the Bruneck Study

Background Whether systemic inflammation is an epiphenomenon of atheroscler osis or whether it is part of the atherosclerosis causal pathway requires f urther study. Design As part of a prospective population survey on the course and aetiolo gy of atherosclerosis, we investigated the effects of plasma on the endothe lial monolayers inducing activation for leukocyte transmigration. Methods An age- and sex-stratified random sample of inhabitants of Bruneck (Italy) with and without atherosclerotic disease aged 50-69 years was selec ted. Carotid arteries were evaluated by duplex sonography at baseline (1990 ). Carotid arteries were re-evaluated for the development of new plaques 5 years later (1995). Frozen plasma samples from baseline were available for a random sample of 152 men. Monolayers of endothelial cells cultured in mic ropore filter insets were pre-treated with plasma, then normal human neutro phils were added to the endothelial cells and subsequent transmigration thr ough the monolayers and micropore filters was measured. Results The endothelial monolayers were activated for transmigration of leu kocytes more potently by plasma from participants with carotid artery plaqu es than participants without it. Increased endothelial activation with plas ma at baseline was associated with the development of new atherosclerotic l esions during a period of 5 years. Conclusions Plasma from individuals with prevalent atherosclerosis of the c arotid arteries activates the endothelium for leukocyte transmigration, sug gesting the presence of systemic pro-inflammatory mediators. In an epidemio logical survey, follow-up data on new lesion formation after 5 years indica ted that plasma-mediated endothelium activation for interaction with leukoc ytes precedes the development of atherosclerotic lesions. (C) 2000 Lippinco tt Williams & Wilkins.