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

Background: Whether systemic inflammation is an epiphenomenon of atherosclerosis or whether it is part of the atherosclerosis causal pathway requires further study.

Design: As part of a prospective population survey on the course and aetiology of atherosclerosis, we investigated the effects of plasma on the endothelial 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 selected. 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 micropore filter insets were pre-treated with plasma, then normal human neutrophils were added to the endothelial cells and subsequent transmigration through the monolayers and micropore filters was measured.

Results: The endothelial monolayers were activated for transmigration of leukocytes more potently by plasma from participants with carotid artery plaques than participants without it. Increased endothelial activation with plasma at baseline was associated with the development of new atherosclerotic lesions during a period of 5 years.

Conclusions: Plasma from individuals with prevalent atherosclerosis of the carotid arteries activates the endothelium for leukocyte transmigration, suggesting the presence of systemic pro-inflammatory mediators. In an epidemiological survey, follow-up data on new lesion formation after 5 years indicated that plasma-mediated endothelium activation for interaction with leukocytes precedes the development of atherosclerotic lesions.