Diabetologia

, Volume 39, Issue 12, pp 1425–1431

Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture

Authors

  • A. Pandolfi
    • Istituto di Fisiopatologia Medica, University of Chieti, Italy
  • L. Iacoviello
    • “Angela Valenti” Thrombosis Pharmacology Laboratory, Istituto di Ricerche Farmacologiche, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
  • F. Capani
    • Istituto di Fisiopatologia Medica, University of Chieti, Italy
  • E. Vitacolonna
    • Istituto di Fisiopatologia Medica, University of Chieti, Italy
  • M. B. Donati
    • “Angela Valenti” Thrombosis Pharmacology Laboratory, Istituto di Ricerche Farmacologiche, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
  • A. Consoli
    • Istituto di Fisiopatologia Medica, University of Chieti, Italy
Originals

DOI: 10.1007/s001250050594

Cite this article as:
Pandolfi, A., Iacoviello, L., Capani, F. et al. Diabetologia (1996) 39: 1425. doi:10.1007/s001250050594

Summary

Hyperglycaemia and hyperinsulinaemia have both been related to accelerated atherosclerosis in non-insulin-dependent diabetes mellitus (NIDDM). Plasma fibrinolytic potential is reduced in NIDDM and it is known that glucose and insulin can modulate plasminogen activator inhibitor (PAI-1) and tissue-plasminogen activator (t-PA) secretion and can therefore regulate local fibrinolysis. Vascular smooth muscle cells (vSMC) play an important role in the development of atherosclerotic lesions; however, the role of insulin and glucose in regulating PAI-1 and t-PA production in vSMC is presently not known. Therefore, we cultured arterial vSMC explanted from human umbilical cords and exposed them to increasing concentrations of glucose (5, 12, 20, 27, 35 mmol/l) or insulin (0.1, 0.5, 1, 10 nmol/l) in a serum free medium. After 24 h, PAI-1 and t-PA antigens and activity were evaluated in the culture medium; in cells exposed to 20 mmol/l glucose and to 0.5 nmol/l insulin PAI-1 gene expression was also evaluated. An increase in PAI-1 antigen was observed at each glucose concentration (by 138, 169, 251 and 357 % as compared to 5 mmol/l glucose) which was paralleled by an increase in PAI-1 activity. t-PA concentration was also increased by glucose but its activity was sharply reduced. An increase in PAI-1 antigen was detected at each insulin level (by 121, 128, 156 and 300 % as compared to no insulin). PAI-1 activity was slightly increased at the lowest insulin concentrations but markedly increased by 10 nmol/l insulin. t-PA antigen was also increased by insulin; however, its activity was markedly reduced at each concentration. As compared to control cells, PAI-1 mRNA was increased by 2.5 and 2.0 fold by 20 mmol/l glucose and 0.5 nmol/l insulin, respectively. We conclude that in human vSMC both glucose and insulin can affect the fibrinolytic balance so as to reduce fibrinolytic potential. This might contribute to decreased local fibrinolysis and thereby might accelerate the atherothrombotic process in NIDDM subjects. [Diabetologia (1996) 39: 1425–1431]

Keywords PAI-1 t-PA fibrinolysis vascular smooth muscle cells glucose insulin.

Copyright information

© Springer-Verlag Berlin Heidelberg 1996