Endothelial cell-associated tissue factor pathway inhibitor (TFPI) antigen in severe nondiabetic obese patients: Effect of hyperinsulinemia

Giuseppe Cella, Roberto Vettor, Alessandra Sbarai, Edoardo Rossi, Ernesto Rampin, Cinzia Macor, Michele Mussap, Mario Plebani, Guido Luzzatto, Antonio Girolami

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Abstract

It has been suggested that the extrinsic coagulation system plays a crucial role in the initiation of blood coagulation in atherosclerotic disease and that TFPI, the inhibitor of the factor VIIa/tissue factor complex, bound to the endothelial cells, could prevent in vivo blood clotting. Because obesity has a role in the pathogenesis of atherosclerotic cardiovascular disease, we measured TFPI antigen plasma levels (ng/mL) by ELISA at baseline and 5 minutes after an IV bolus of 20 IU/kg body weight of unfractionated commercial mucous heparin in 12 obese patients with a mean body mass index (BMI) of 41.4 ± 1.4 kg/m2 and 14 normal-weight control subjects (BMI 23.1 ± 1.3 kg/m2). All subjects were submitted to an OGTT. The obese patients displayed a normal glucose tolerance. However, they had a different glucose-induced hyperinsulinemia (14.9 ± 2.0 versus 7.8 ± 0.8 mU/L, p <0.01). Total serum cholesterol did not differ between controls and obese patients, whereas plasma triglycerides were higher in the latter group. Basal TFPI antigen plasma levels were similar in obese and controls (83.8 ± 5.0 versus 77.7 ± 3.5 ng/mL, p = N.S.). In contrast, after heparin a significantly lower rise in TFPI antigen plasma levels was observed in obese patients (319.3 ± 37.9 ng/mL) as compared to controls (511.2 ± 43.4 ng/mL) (p <0.003). Moreover, a significant inverse correlation was found between the heparin-stimulated TFPI antigen plasma levels and both BMI and basal plasma insulin concentrations. Thus, the link between insulin level and endothelial cell-associated TFPI could at least partially explain why obese patients are more prone to develop cardiovascular disorders.

Original languageEnglish
Pages (from-to)129-134
Number of pages6
JournalSeminars in Thrombosis and Hemostasis
Volume23
Issue number2
Publication statusPublished - 1997

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Keywords

  • Heparin
  • Hyperinsulinemia
  • Lipids
  • Obesity
  • TFPI

ASJC Scopus subject areas

  • Hematology

Cite this

Cella, G., Vettor, R., Sbarai, A., Rossi, E., Rampin, E., Macor, C., Mussap, M., Plebani, M., Luzzatto, G., & Girolami, A. (1997). Endothelial cell-associated tissue factor pathway inhibitor (TFPI) antigen in severe nondiabetic obese patients: Effect of hyperinsulinemia. Seminars in Thrombosis and Hemostasis, 23(2), 129-134.