Selective disruption of endothelial barrier function in culture by pure fatty acids and fatty acids derived from animal and plant fats

Endothelial cell integrity has been suggested to play a role in the development of atherosclerosis. The effects of fatty acids on endothelial barrier function were tested by measuring albumin transport across endothelial monolayers cultured on polycarbonate filters. Compared with control cultures, a 24-h exposure to 90 μmol/L lauric (12:0) and linoleic acid (18:2) but not to butyric (4:0), hexanoic (6:0), octanoic (8:0), decanoic (10:0), myristic (14:0), palmitic (16:0) or stearic acid (18:0) caused an increase in albumin transfer across endothelial monolayers. Selective enrichment of a 'physiological' serum fatty acid mixture (FA-Mix; 90 μmol/L) with 90 μmol/L of 12:0 or 18:2 significantly increased albumin transfer, whereas enrichment with 90 μmol/L of 4:0, 16:0 or 18:0 significantly decreased albumin transfer relative to 180 μmol/L FA-Mix. Only 12:0- or 18:2-treated cultures showed increased Ca⁺⁺ -ATPase activity and the presence of lipid droplets. Fatty acids (60 μmol/L) extracted from butter fat and beef tallow had no effect on albumin transfer, whereas fatty acids extracted from chicken fat and corn oil consistently disrupted endothelial barrier function. This fat-induced disruption of endothelial barrier function seems to be related to the amount of 18:2 present in each fat source. These data indicate that unsaturated fats cause cellular perturbations that result in a decrease in endothelial barrier function in this model system, and that high dietary levels of unsaturated fats may be detrimental to cell integrity.