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 de velopment of atherosclerosis. The effects of fatty acids on endothelia l barrier function were tested by measuring albumin transport across e ndothelial monolayers cultured on polycarbonate filters. Compared with control cultures, a 24-h exposure to 90 mumol/L lauric (12:0) and lin oleic 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 aci d (18:0) caused an increase in albumin transfer across endothelial mon olayers. Selective enrichment of a ''physiological'' serum fatty acid mixture (FA-Mix; 90 mumol/L) with 90 mumol/L of 12:0 or 18:2 significa ntly increased albumin transfer, whereas enrichment with 90 mumol/L of 4:0, 16:0 or 18:0 significantly decreased albumin transfer relative t o 180 mumol/L FA-Mix. Only 12:0- or 18:2-treated cultures showed incre ased Ca++-ATPase activity and the presence of lipid droplets. Fatty ac ids (60 mumol/L) extracted from butter fat and beef tallow had no effe ct on albumin transfer, whereas fatty acids extracted from chicken fat and corn oil consistently disrupted endothelial barrier function. Thi s fat-induced disruption of endothelial barrier function seems to be r elated to the amount of 18:2 present in each fat source. These data in dicate that unsaturated fats cause cellular perturbations that result in a decrease in endothelial barrier function in this model system, an d that high dietary levels of unsaturated fats may be detrimental to c ell integrity.