Fluvastatin inhibits pai-1 antigen secretion in human endothelial cells

L. Mussoni, C. Banfi, L. Tremoli

Research output: Contribution to journalArticle

Abstract

Fluvastatin (Sandoz, Basel) is a newly developed synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which effectively reduces cholesterol levels in hypercholesterolemic patients, has been shown to affect also several cellular functions, (i.e. cell growth, chemotaxis, IL-8 release, tissue factor expression). In this study we have examined the effects of Fluvastatin on the secretion of plasminogen activator inhibitor type-1 (PAI-1) in cultured human endothelial cells (HUVEC). Confluent HUVEC were incubated for 24 hours with medium containing 15% PCS and Fluvastatin (0.1-2.5μmol/L). Cells were then challenged with LPS (10 μg/ml) or PMA (100 nM) for further 16 hours in the presence of Fluvastatin and 2.5% FCS. Fluvastatin decreased PAI-1 antigen release in a dose-dependent manner both in unstimulated and LPS or PMA stimulated cells. The effect of Fluvastatin was more pronounced in cells stimulated with PMA than with LPS. At the highest concentration used, (2.5μmol/), Fluvastatin reduced the secretion of PAI-1 by 84% in unstimulated cells and by 32% and 67% in LPS and PMA stimulated cells respectively. The inhibitory effect of Fluvastatin on PAI-1 antigen was fully reversible by coincubation with mevalonate (100μmol/L) or all-frans-geranylgeraniol (10μmol/L) but not by farnesol. These data indicate that Fluvastatin, besides its effect on plasma lipids, mediates the reduction in PAI-1 antigen levels, a "marker" of endothelial cells dysfunction, throughout the inhibition of mevalonate biosynthesis.

Original languageEnglish
Pages (from-to)73
Number of pages1
JournalFibrinolysis
Volume10
Issue numberSUPPL. 3
Publication statusPublished - 1996

Fingerprint

fluvastatin
Endothelial Cells
Antigens
Plasminogen Activator Inhibitor 1
Mevalonic Acid
Farnesol
Thromboplastin
Chemotaxis

ASJC Scopus subject areas

  • Hematology

Cite this

Fluvastatin inhibits pai-1 antigen secretion in human endothelial cells. / Mussoni, L.; Banfi, C.; Tremoli, L.

In: Fibrinolysis, Vol. 10, No. SUPPL. 3, 1996, p. 73.

Research output: Contribution to journalArticle

Mussoni, L, Banfi, C & Tremoli, L 1996, 'Fluvastatin inhibits pai-1 antigen secretion in human endothelial cells', Fibrinolysis, vol. 10, no. SUPPL. 3, pp. 73.
Mussoni, L. ; Banfi, C. ; Tremoli, L. / Fluvastatin inhibits pai-1 antigen secretion in human endothelial cells. In: Fibrinolysis. 1996 ; Vol. 10, No. SUPPL. 3. pp. 73.
@article{4c58119d21964c99bfeb74bbc11baf4a,
title = "Fluvastatin inhibits pai-1 antigen secretion in human endothelial cells",
abstract = "Fluvastatin (Sandoz, Basel) is a newly developed synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which effectively reduces cholesterol levels in hypercholesterolemic patients, has been shown to affect also several cellular functions, (i.e. cell growth, chemotaxis, IL-8 release, tissue factor expression). In this study we have examined the effects of Fluvastatin on the secretion of plasminogen activator inhibitor type-1 (PAI-1) in cultured human endothelial cells (HUVEC). Confluent HUVEC were incubated for 24 hours with medium containing 15{\%} PCS and Fluvastatin (0.1-2.5μmol/L). Cells were then challenged with LPS (10 μg/ml) or PMA (100 nM) for further 16 hours in the presence of Fluvastatin and 2.5{\%} FCS. Fluvastatin decreased PAI-1 antigen release in a dose-dependent manner both in unstimulated and LPS or PMA stimulated cells. The effect of Fluvastatin was more pronounced in cells stimulated with PMA than with LPS. At the highest concentration used, (2.5μmol/), Fluvastatin reduced the secretion of PAI-1 by 84{\%} in unstimulated cells and by 32{\%} and 67{\%} in LPS and PMA stimulated cells respectively. The inhibitory effect of Fluvastatin on PAI-1 antigen was fully reversible by coincubation with mevalonate (100μmol/L) or all-frans-geranylgeraniol (10μmol/L) but not by farnesol. These data indicate that Fluvastatin, besides its effect on plasma lipids, mediates the reduction in PAI-1 antigen levels, a {"}marker{"} of endothelial cells dysfunction, throughout the inhibition of mevalonate biosynthesis.",
author = "L. Mussoni and C. Banfi and L. Tremoli",
year = "1996",
language = "English",
volume = "10",
pages = "73",
journal = "Fibrinolysis and Proteolysis",
issn = "1369-0191",
publisher = "Churchill Livingstone",
number = "SUPPL. 3",

}

TY - JOUR

T1 - Fluvastatin inhibits pai-1 antigen secretion in human endothelial cells

AU - Mussoni, L.

AU - Banfi, C.

AU - Tremoli, L.

PY - 1996

Y1 - 1996

N2 - Fluvastatin (Sandoz, Basel) is a newly developed synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which effectively reduces cholesterol levels in hypercholesterolemic patients, has been shown to affect also several cellular functions, (i.e. cell growth, chemotaxis, IL-8 release, tissue factor expression). In this study we have examined the effects of Fluvastatin on the secretion of plasminogen activator inhibitor type-1 (PAI-1) in cultured human endothelial cells (HUVEC). Confluent HUVEC were incubated for 24 hours with medium containing 15% PCS and Fluvastatin (0.1-2.5μmol/L). Cells were then challenged with LPS (10 μg/ml) or PMA (100 nM) for further 16 hours in the presence of Fluvastatin and 2.5% FCS. Fluvastatin decreased PAI-1 antigen release in a dose-dependent manner both in unstimulated and LPS or PMA stimulated cells. The effect of Fluvastatin was more pronounced in cells stimulated with PMA than with LPS. At the highest concentration used, (2.5μmol/), Fluvastatin reduced the secretion of PAI-1 by 84% in unstimulated cells and by 32% and 67% in LPS and PMA stimulated cells respectively. The inhibitory effect of Fluvastatin on PAI-1 antigen was fully reversible by coincubation with mevalonate (100μmol/L) or all-frans-geranylgeraniol (10μmol/L) but not by farnesol. These data indicate that Fluvastatin, besides its effect on plasma lipids, mediates the reduction in PAI-1 antigen levels, a "marker" of endothelial cells dysfunction, throughout the inhibition of mevalonate biosynthesis.

AB - Fluvastatin (Sandoz, Basel) is a newly developed synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, which effectively reduces cholesterol levels in hypercholesterolemic patients, has been shown to affect also several cellular functions, (i.e. cell growth, chemotaxis, IL-8 release, tissue factor expression). In this study we have examined the effects of Fluvastatin on the secretion of plasminogen activator inhibitor type-1 (PAI-1) in cultured human endothelial cells (HUVEC). Confluent HUVEC were incubated for 24 hours with medium containing 15% PCS and Fluvastatin (0.1-2.5μmol/L). Cells were then challenged with LPS (10 μg/ml) or PMA (100 nM) for further 16 hours in the presence of Fluvastatin and 2.5% FCS. Fluvastatin decreased PAI-1 antigen release in a dose-dependent manner both in unstimulated and LPS or PMA stimulated cells. The effect of Fluvastatin was more pronounced in cells stimulated with PMA than with LPS. At the highest concentration used, (2.5μmol/), Fluvastatin reduced the secretion of PAI-1 by 84% in unstimulated cells and by 32% and 67% in LPS and PMA stimulated cells respectively. The inhibitory effect of Fluvastatin on PAI-1 antigen was fully reversible by coincubation with mevalonate (100μmol/L) or all-frans-geranylgeraniol (10μmol/L) but not by farnesol. These data indicate that Fluvastatin, besides its effect on plasma lipids, mediates the reduction in PAI-1 antigen levels, a "marker" of endothelial cells dysfunction, throughout the inhibition of mevalonate biosynthesis.

UR - http://www.scopus.com/inward/record.url?scp=33846660882&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846660882&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33846660882

VL - 10

SP - 73

JO - Fibrinolysis and Proteolysis

JF - Fibrinolysis and Proteolysis

SN - 1369-0191

IS - SUPPL. 3

ER -