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 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.
Byrne
C D
CD
University Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, UK. cdtb@mole.bio.cam.ac.uk
Wareham
N J
NJ
Martensz
N D
ND
Humphries
S E
SE
Metcalfe
J C
JC
Grainger
D J
DJ
D000368:Aged; D000483:Alleles; D015992:Body Mass Index; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D019518:Postprandial Period; D011401:Promoter Regions, Genetic; D016212:Transforming Growth Factor beta / Q000097:blood*; D014280:Triglycerides / Q000097:blood
D004041:Dietary Fats; D017395:Plasminogen Activator Inhibitor 1; D015849:Plasminogen Inactivators; D016212:Transforming Growth Factor beta; D014280:Triglycerides