Relationship between fibrinolytic and metabolic variables: a study in patients attending a lipid clinic.
We investigated the relationship between plasma levels of metabolic and fibrinolytic variables in 163 fasted patients attending a lipid clinic. Of these patients, 118 had hypertriglyceridaemia (HTG) and 45 had normotriglyceridaemia (NTG). In HTG, basal fibrinolytic activity, ie tissue plasminogen activator (t-PA) activity, was impaired as a result of high plasminogen activator inhibitor type 1 (PAI-1) antigen and activity. Multiple stepwise regression analysis identified insulin and triglyceride levels as independent determinants of plasma PAI-1 levels (R2 = 0.18; P = 0.0001). When the patients were stratified into tertiles according to their levels of triglyceride and insulin, PAI-1 antigen levels were found to increase with rising levels of triglyceride in each insulin tertile. In contrast, the increase of PAI-1 with rising insulin levels was evident in the highest triglyceride tertile. In addition, subjects in the lowest tertile of both triglyceride and insulin had the lowest PAI-1 antigen levels, and subjects in the highest tertile of both triglyceride and insulin had the highest levels of PAI-1. Both basal and stimulated levels of t-PA antigen were significantly higher in HTG than in NTG. Multiple stepwise regression analysis identified triglyceride level as the sole major determinant of t-PA antigen levels (R2 = 0.13; P = 0.00003). The observation that both insulin and triglycerides correlate with PAI-1, whereas triglycerides were involved only in the increased secretion of t-PA, suggests that these two proteins are regulated by different mechanisms.
Mussoni
L
L
Institute of Pharmacological Sciences and E Grossi Paoletti Center, University of Milan, Italy.
Baldassarre
D
D
Mannucci
L
L
Sirtori
C R
CR
Tremoli
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000554:Ambulatory Care Facilities; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D007328:Insulin / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D010960:Plasminogen Activators / Q000097:blood*; D012016:Reference Values; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D010959:Tissue Plasminogen Activator / Q000097:blood*; D014280:Triglycerides / Q000096:biosynthesis*
D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator