Previous studies have shown that plasminogen activator inhibitor type 1 (PAI-1) levels are elevated in plasma of patients with hypertriglyceridemia. In the present study we have evaluated the effects of very low density lipoproteins (VLDL) isolated from plasma ot normal donors on PAI-1 synthesis by HepG2 cells. Cells (4x1Q6) incubated in serum free medium for 14-16 hours released 11.2 ±2.4 SE ng/ml (n=8) PAI-1 antigen determined by ELlSA. Levels of PAI-1 antigen in supernatants of HepG2 cells incubated with 100 µg protein/ml VLDL were increased by two•fold (22.B±S.3 SE ng/ml) (n=9). The increases in PAI-1 synthesis observed in the presence of VLDL were accompanied by concomitant changes in PAI-1 mRNA levels as determined by Northern blot analysis. In particular, 100 µg/ml VLDL increased three-fold the cellular levels of the 2.2 Kb PAI-1 mRNA species (p<0.001. n=7). whereas levels ot the 3.2 Kb PAI-1 mRNA remained essentially unchanged or even decreased. Therefore. 2.2/3.2 Kb PAI-1 mRNA ratio increased in VLDL treated samples Cycloheximide (25 µg/ml) changed the ratio between the two PAI-1 mRNAs in the favour of the 3.2 Kb PAI-1 mRNA species in VLDL treated cells. Time•course experiments showed that the effects of VLDL on the 2.2 Kb PAI-1 mRNA were evident after 9 hour incubation of the lipoproteins with cells. When VLDL were incubated with HepG2 in the presence of a concentration of insulin (135 nM) known to increase PAI-1 synthesis in this cell type. additive effects of VLDL on PAI-1 mRNA expression and on PAI-1 antigen release were observed. The effect of triglyceride rich lipoproteins on PAI-1 synthesis by HepG2 may be of importance in determining the increased levels of circulating PAI-1 described in hypertriglyceridemic patients.

Plasminogen activator inhibitor type-1 mRNA expression is increased by triglyceride rich lipoproteins in human hepatoma cells / L. Mussoni, L. Sironi, L. Prati, D. Baldassarre, M. Camera, E. Tremoli. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - 69:6(1993), pp. 548-548. ((Intervento presentato al 14. convegno Congress of the International society on Thrombosis and Haemostasis tenutosi a New York, USA nel 1993.

Plasminogen activator inhibitor type-1 mRNA expression is increased by triglyceride rich lipoproteins in human hepatoma cells

L. Mussoni
Primo
;
L. Sironi;D. Baldassarre;M. Camera
Penultimo
;
E. Tremoli
Ultimo
1993

Abstract

Previous studies have shown that plasminogen activator inhibitor type 1 (PAI-1) levels are elevated in plasma of patients with hypertriglyceridemia. In the present study we have evaluated the effects of very low density lipoproteins (VLDL) isolated from plasma ot normal donors on PAI-1 synthesis by HepG2 cells. Cells (4x1Q6) incubated in serum free medium for 14-16 hours released 11.2 ±2.4 SE ng/ml (n=8) PAI-1 antigen determined by ELlSA. Levels of PAI-1 antigen in supernatants of HepG2 cells incubated with 100 µg protein/ml VLDL were increased by two•fold (22.B±S.3 SE ng/ml) (n=9). The increases in PAI-1 synthesis observed in the presence of VLDL were accompanied by concomitant changes in PAI-1 mRNA levels as determined by Northern blot analysis. In particular, 100 µg/ml VLDL increased three-fold the cellular levels of the 2.2 Kb PAI-1 mRNA species (p<0.001. n=7). whereas levels ot the 3.2 Kb PAI-1 mRNA remained essentially unchanged or even decreased. Therefore. 2.2/3.2 Kb PAI-1 mRNA ratio increased in VLDL treated samples Cycloheximide (25 µg/ml) changed the ratio between the two PAI-1 mRNAs in the favour of the 3.2 Kb PAI-1 mRNA species in VLDL treated cells. Time•course experiments showed that the effects of VLDL on the 2.2 Kb PAI-1 mRNA were evident after 9 hour incubation of the lipoproteins with cells. When VLDL were incubated with HepG2 in the presence of a concentration of insulin (135 nM) known to increase PAI-1 synthesis in this cell type. additive effects of VLDL on PAI-1 mRNA expression and on PAI-1 antigen release were observed. The effect of triglyceride rich lipoproteins on PAI-1 synthesis by HepG2 may be of importance in determining the increased levels of circulating PAI-1 described in hypertriglyceridemic patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/192064
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