Insulin resistance causes impaired vasodilation and hypofibrinolysis in young women with polycystic ovary syndrome.
BACKGROUND
Insulin resistance, a novel cardiovascular risk factor, is often associated with increased plasminogen activator inhibitor-1 levels and impaired vasodilation. Insulin infusion in the forearm induces plasminogen activator inhibitor-1 and tissue plasminogen activator expression and endothelium-dependent vasodilation in normal subjects. The present study explores the relationship between insulin-induced vasodilatory and fibrinolytic properties of the endothelium in women with polycystic ovary syndrome, frequently affected by insulin resistance and early atherosclerosis.


METHODS
Metabolic, hormonal and fibrinolytic parameters were evaluated in 64 patients with polycystic ovary syndrome (19 insulin-resistant and 45 insulin-sensitive) and in 25 controls. In 16 women with polycystic ovary syndrome, 8 insulin-resistant and 8 insulin-sensitive, blood flow, plasminogen activator inhibitor-1 and tissue plasminogen activator expression were evaluated during insulin infusion into the forearm.


RESULTS
Elevated basal plasminogen activator inhibitor-1 levels were found in women with polycystic ovary syndrome, correlating directly with insulin levels. Plasminogen activator inhibitor-1 expression increased during insulin infusion in all women with polycystic ovary syndrome, but was delayed and sustained in insulin-resistant patients (p<0.01). Vasodilatory response to insulin was blunted (p<0.01) and tissue plasminogen activator expression abolished in insulin-resistant patients (p<0.01).


CONCLUSIONS
Our study demonstrates that women with polycystic ovary syndrome and insulin resistance show a blunted endothelial-dependent vasodilation. The impaired endothelial release of tissue-plasminogen activator and the sustained plasminogen activator inhibitor-1 release during insulin infusion suggest a hypofibrinolytic state in PCOS patients with insulin resistance. This hemodynamic and fibrinolytic derangement may contribute to the pathogenesis of early atherosclerosis in insulin resistance.
Carmassi
Franco
F
Department of Internal Medicine, University of Pisa, via Roma 67, I-56126 Pisa, Italy. f.carmassi@int.med.unipi.it
De Negri
Ferdinando
F
Fioriti
Roberta
R
De Giorgi
Antonio
A
Giannarelli
Chiara
C
Fruzzetti
Franca
F
Pedrinelli
Roberto
R
Dell'Omo
Giulia
G
Bersi
Chiara
C
D000328:Adult; D001161:Arteriosclerosis / Q000209:etiology; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D010959:Tissue Plasminogen Activator / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator