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Adhesion and migration of mononuclear leukocytes to the vascular intima play an important role in the pathogenesis of atherosclerosis. Adhesion molecules VCAM-I and ICAM-I are the mediators of this process. Short-chain fatty acids (SCFAs) produced during bacterial fermentation of dietary fibre in the large bowel are suggested to exert a beneficial anti-atherosclerotic action. The purpose of this study was to investigate whether propionic acid and butyric acid can have an ability to protect endothelial cells against their dysfunction induced by oxidised LDL (ox-LDL) and the related increased adhesiveness for monocytes and lymphocytes. The tests were performed on endothelial cells isolated from human umbilical veins (HUVEC) and incubated with ox-LDL (100 mg/ml) separately or in combination with propionic acid or butyric acid in concentration within the range of 1.0 to 10 mmol/L. VCAM-1 and ICAM-1 expression was measured either by flow cytometry (protein) or by RT-PCR (mRNA). Propionic acid and butyric acid were found to inhibit significantly (ANOVA p < 0.001, n = 8) ox-LDL-induced VCAM-1 and ICAM-1 expression both at the protein as well as the mRNA levels through their effect on NF-kB-dependent transcription mechanisms, and thus to lower the adhesiveness of endothelial cells for monocytes and lymphocytes. Our results indicate the existence of new mechanisms of anti-inflammatory and anti-atherosclerotic action of SCFAs.
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J. Vasc. Biol. 42, Sup:2 (2005) pp122-123