The effects of native and acetylated low density lipoproteins (LDLs and acetyl-LDLs, respectively) on the release of plasminogen activator inhibitor type 1 (PAI-1) by cultured human umbilical vein endothelial cells (ECs) were evaluated. LDL and acetyl-LDL incubated with ECs for 16-18 hours increased the PAI-1 antigen levels in conditioned medium. At a concentration of 100 μg/mL, LDL and acetyl-LDL increased PAI-1 by 10.8 and 12.0 ng/mL, respectively (p<0.05 and p<0.01 versus control). The increases in PAI-1 antigen levels exerted by the lipoproteins paralleled the changes in PAI-1 activity. The effect of LDL and acetyl-LDL was concentration dependent and specific for PAI-1 because tissue-type plasminogen activator and expression of procoagulant activity were not affected by either lipoprotein. In addition, total protein synthesis evaluated in [35S]methionine-labeIed ECs was not affected, and studies with cycloheximide showed that the effect of LDL and acetyl-LDL on PAI-1 release was due to de novo protein synthesis. Experiments using the C7 monoclonal antibody against the LDL receptor and binding-defective LDL indicated that the effect of LDL on the synthesis of PAI-1 was not dependent on the interaction of the LDLs with their specific receptors. Finally, extensive oxidation of LDL prevented and even reversed the effect of LDL on PAI-1 release bv ECs. It is concluded that LDL specifically increases the svnthesis of PAI-1 by ECs with mechanisms that are not receptor mediated.

Increased synthesis of plasminogen activator inhibitor-1 by cultured human endothelial cells exposed to native and modified LDLs: An LDL receptor-independent phenomenon / Tremoli, E.; Camera M., A; Maderna, P; Sironi, L; Prati, L.; Colli, S; Piovella, F.; Bernini, F; Corsini, A.; Mussoni, L.. - In: ARTERIOSCLEROSIS AND THROMBOSIS. - ISSN 1049-8834. - 13:3(1993), pp. 338-346. [10.1161/01.ATV.13.3.338]

Increased synthesis of plasminogen activator inhibitor-1 by cultured human endothelial cells exposed to native and modified LDLs: An LDL receptor-independent phenomenon

Bernini F;
1993

Abstract

The effects of native and acetylated low density lipoproteins (LDLs and acetyl-LDLs, respectively) on the release of plasminogen activator inhibitor type 1 (PAI-1) by cultured human umbilical vein endothelial cells (ECs) were evaluated. LDL and acetyl-LDL incubated with ECs for 16-18 hours increased the PAI-1 antigen levels in conditioned medium. At a concentration of 100 μg/mL, LDL and acetyl-LDL increased PAI-1 by 10.8 and 12.0 ng/mL, respectively (p<0.05 and p<0.01 versus control). The increases in PAI-1 antigen levels exerted by the lipoproteins paralleled the changes in PAI-1 activity. The effect of LDL and acetyl-LDL was concentration dependent and specific for PAI-1 because tissue-type plasminogen activator and expression of procoagulant activity were not affected by either lipoprotein. In addition, total protein synthesis evaluated in [35S]methionine-labeIed ECs was not affected, and studies with cycloheximide showed that the effect of LDL and acetyl-LDL on PAI-1 release was due to de novo protein synthesis. Experiments using the C7 monoclonal antibody against the LDL receptor and binding-defective LDL indicated that the effect of LDL on the synthesis of PAI-1 was not dependent on the interaction of the LDLs with their specific receptors. Finally, extensive oxidation of LDL prevented and even reversed the effect of LDL on PAI-1 release bv ECs. It is concluded that LDL specifically increases the svnthesis of PAI-1 by ECs with mechanisms that are not receptor mediated.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2839265
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