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Increased PAI activity and PAI-1 antigen occurring with an oral fat load: associations with PAI-1 genotype and plasma active TGF-beta levels.

Byrne, CD; Wareham, NJ; Martensz, ND; Humphries, SE; Metcalfe, JC; Grainger, DJ; (1998) Increased PAI activity and PAI-1 antigen occurring with an oral fat load: associations with PAI-1 genotype and plasma active TGF-beta levels. Atherosclerosis , 140 (1) pp. 45-53.

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Abstract

Whether the post-prandial lipemic response is linked to potentially pro-atherogenic and/or prothrombotic changes in plasminogen activator inhibitor (PAI) and transforming growth factor-beta (TGF-beta) is uncertain. The aim of our study was to determine whether PAI-1 antigen and PAI activity were elevated during post-prandial lipemia following a standard fat tolerance test. We also investigated changes in TGF-beta1 antigen and TGF-beta activity, to determine whether changes in TGF-beta activity were associated with changes in PAI measurements. Lastly, the influence of genotype at a common insertion/deletion polymorphism in the PAI-1 promoter on changes in PAI activity and PAI-1 antigen was examined. Fat tolerance tests were undertaken in 57 healthy middle-aged men to investigate associations between plasma concentrations of lipoproteins, 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 < 0.0001). Increases in PAI-I antigen and PAI activity varied markedly between individuals. To investigate these heterogeneous responses we examined whether genotype at the common insertion/deletion polymorphism of the PAI-1 promoter accounted for these differences. Individuals with at least one 4G (deletion) allele showed potentially pro-atherogenic changes in both PAI-1 and TGF-beta, compared to individuals who were homozygous 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 in the PAI-1 promoter.

Type: Article
Title: Increased PAI activity and PAI-1 antigen occurring with an oral fat load: associations with PAI-1 genotype and plasma active TGF-beta levels.
Location: Ireland
Keywords: Aged, Alleles, Body Mass Index, Dietary Fats, Genotype, Humans, Male, Middle Aged, Plasminogen Activator Inhibitor 1, Plasminogen Inactivators, Postprandial Period, Promoter Regions, Genetic, Transforming Growth Factor beta, Triglycerides
URI: http://discovery.ucl.ac.uk/id/eprint/97268
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