Plasma plasminogen activator inhibitor-1 in angina pectoris. Influence of plasma insulin and acute-phase response.
Plasminogen activator inhibitor-1 (PAI-1) is an important physiological inhibitor of fibrinolysis. It circulates in blood both in free active form and in inactive form complexed with tissue type plasminogen activator (t-PA). Control mechanisms for its synthesis and release from hepatocytes and endothelial cells are important in the pathogenesis of thrombosis. Possible risk factors for myocardial infarction include high insulin and PAI-1 levels, which correlate with one another in healthy subjects, and fibrinogen, which together with PAI-1, is an acute-phase reactant. We therefore studied the interrelationships between PAI-1, plasma insulin, and acute-phase proteins in 67 patients with angina pectoris. Plasma insulin correlated strongly (r = 0.59, p less than 0.001) with PAI activity, free PAI-1 antigen (r = 0.60, p less than 0.001), and total PAI-1 antigen (r = 0.58, p less than 0.001). The acute-phase proteins, fibrinogen and C-reactive protein, correlated significantly with t-PA antigen, total PAI-1 antigen, and PAI-1/t-PA complexes but not with PAI activity or free PAI-1. The results suggest that insulin stimulates synthesis and release of free PAI-1 (probably via hepatocytes as previously shown with cell culture) and that endothelial cell synthesis and release of t-PA, together with PAI-1, reflects a nonspecific acute-phase response to chronic vascular disease. Hyperinsulinemia found in patients with angina pectoris could play a role in the development of myocardial infarction via the induction of high plasma PAI-1 activity.
Juhan-Vague
I
I
University Hospital Timone, Marseille, France.
Alessi
M C
MC
Joly
P
P
Thirion
X
X
Vague
P
P
Declerck
P J
PJ
Serradimigni
A
A
Collen
D
D
D000209:Acute-Phase Proteins / Q000097:blood*; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005342:Fibrinolysis; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator / Q000097:blood
D000209:Acute-Phase Proteins; D006023:Glycoproteins; D007328:Insulin; D015849:Plasminogen Inactivators; D005340:Fibrinogen; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator