Constitutive biosynthesis of plasminogen activator inhibitor type-1 (PAI-1) by cultured human aortic endothelial cells independent of insulin.
Coron Artery Dis
; 4(8): 713-9, 1993 Aug.
Article
em En
| MEDLINE
| ID: mdl-8261243
ABSTRACT
BACKGROUND:
Both tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) are synthesized by vascular endothelium, whereas hepatocytes synthesize PAI-1 but not t-PA. Non-insulin-dependent diabetes mellitus (NIDDM) is associated with decreased fibrinolytic activity in blood secondary to increased PAI-1 activity, and the increase in PAI-1 activity is correlated with the magnitude of elevation of plasma immunoreactive insulin. To determine whether the increased PAI-1, known to be associated with accelerated coronary artery disease in non-diabetic subjects, is a consequence of direct effects of insulin on endothelial cells, we performed the present study with primary cultures of human aortic endothelial cells.METHODS:
Endothelial cells isolated from human aortas from donor hearts for transplantation were grown to confluence and exposed to selected concentrations of agonists. Accumulation of t-PA and PAI-1 in conditioned media was quantified, as was PAI-1 activity.RESULTS:
Insulin at pharmacologic concentrations did not alter either PAI-1 or t-PA production by the human aortic endothelial cells, although insulin stimulated PAI-1 synthesis in human hepatoma (Hep G2) cells as expected. Transforming growth factor-beta (TGF-beta) stimulated endothelial cell PAI-1 production markedly, indicating that the cells could respond positively to stimulation in vitro. PAI-1 activity in the conditioned media was zero under all conditions, which was indicative of the rapid inactivation and degradation of PAI-1 known to occur in media devoid of vitronectin.CONCLUSIONS:
The decreased fibrinolytic activity in blood seen in patients with NIDDM appears to reflect direct effects of insulin or its precursor on hepatocytes rather than on endothelial cells.
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Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Inibidor 1 de Ativador de Plasminogênio
/
Insulina
Limite:
Adolescent
/
Adult
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
1993
Tipo de documento:
Article