INCREASED PAI ACTIVITY AND PAI-1 ANTIGEN OCCURRING WITH AN ORAL FAT LOAD - ASSOCIATIONS WITH PAI-1 GENOTYPE AND PLASMA ACTIVE TGF-BETA LEVELS

Whether the post-prandial lipemic response is linked to potentially pr o-atherogenic and/or prothrombotic changes in plasminogen activator in hibitor (PAI) and transforming growth factor-beta (TGF-beta) is uncert ain. The aim of our study was to determine whether PAI-1 antigen and P AI activity were elevated during post-prandial lipemia following a sta ndard fat tolerance test. We also investigated changes in TGF-beta 1 a ntigen and TCF-beta activity, to determine whether changes in TGF-beta activity were associated with changes in PAI measurements. Lastly, th e influence of genotype at a common insertion/deletion polymorphism in the PAI-1 promoter on changes in PAI activity and PAI-1 antigen was e xamined. Fat tolerance tests were undertaken in 57 healthy middle-aged men to investigate associations between plasma concentrations of lipo proteins, PAI (antigen and activity) and TGF-beta. PAI-1 concentration increased by 76% after 8 h (P < 0.0001). PAI: activity also increased by 64% (P = 0.0054) and TGF-beta activity decreased by 10% (P < 0.000 1). Increases in PAI-1 antigen and PAI activity varied markedly betwee n individuals. To investigate these heterogeneous responses we examine d whether genotype at the common insertion/deletion polymorphism of th e PAI-1 promoter accounted for these differences. individuals with at least one 4G (deletion) allele showed potentially pro-atherogenic chan ges in both PAI-I and TGF-beta, compared to individuals who were homoz ygous for the 5G (insertion) allele. In conclusion, increased PAI and decreased TGF-beta activity occur during a fat tolerance test and this effect may be modulated by a common insertion/deletion polymorphism i n the PAI-1 promoter. (C) 1998 Elsevier Science Ireland Ltd. All right s reserved.