Abstract
The major relation existing between cell growth, migration and cholesterol homeostasis prompted us to investigate the effect of the new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin (BAY W 6228) on these cellular events. The molecule inhibited in a dose-dependent manner the migration and the replication (evaluated as cell number and nuclear incorporation of 3H-thymidine) of rat arterial SMC with IC50 values of 2.7 μM and 0.5 μM, respectively. Among the tested statins BAY W 6228 resulted to be the most potent inhibitor of cholesterol synthesis and cell proliferation. Conditions producing 80-90% inhibition of cholesterol synthesis correlate with approximately 50% inhibition of cell growth. Similar results were obtained in SMC from human femoral artery. The in vitro inhibition of cell migration and proliferation induced by BAY W 6228 (80% decrease) was completely prevented by the addition of mevalonate and partially prevented (60-80%) by farnesol and geranylgeraniol, confirming the specific role of isoprenoid metabolites-probably through a prenylated protein(s)-in regulating these cellular events. The present results provide evidence that BAY W 6228 interferes, at least in vivo, with smooth muscle cells migration and proliferation, major processes involved in atherogenesis.
| Original language | English |
|---|---|
| Pages (from-to) | 55-61 |
| Number of pages | 7 |
| Journal | Pharmacological Research |
| Volume | 33 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1996 |
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Keywords
- BAY W 6228
- Cerivastatin
- Isoprenoids
- Myocyte migration
- Myocyte proliferation
- Statins
ASJC Scopus subject areas
- Pharmacology
Cite this
Effect of the new HMG-CoA reductase inhibitor cerivastatin (BAY W 6228) on migration, proliferation and cholesterol synthesis in arterial myocytes. / Corsini, Alberto; Arnaboldi, L.; Raiteri, M.; Quarato, P.; Faggiotto, A.; Paoletti, R.; Fumagalli, R.
In: Pharmacological Research, Vol. 33, No. 1, 01.1996, p. 55-61.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of the new HMG-CoA reductase inhibitor cerivastatin (BAY W 6228) on migration, proliferation and cholesterol synthesis in arterial myocytes
AU - Corsini, Alberto
AU - Arnaboldi, L.
AU - Raiteri, M.
AU - Quarato, P.
AU - Faggiotto, A.
AU - Paoletti, R.
AU - Fumagalli, R.
PY - 1996/1
Y1 - 1996/1
N2 - The major relation existing between cell growth, migration and cholesterol homeostasis prompted us to investigate the effect of the new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin (BAY W 6228) on these cellular events. The molecule inhibited in a dose-dependent manner the migration and the replication (evaluated as cell number and nuclear incorporation of 3H-thymidine) of rat arterial SMC with IC50 values of 2.7 μM and 0.5 μM, respectively. Among the tested statins BAY W 6228 resulted to be the most potent inhibitor of cholesterol synthesis and cell proliferation. Conditions producing 80-90% inhibition of cholesterol synthesis correlate with approximately 50% inhibition of cell growth. Similar results were obtained in SMC from human femoral artery. The in vitro inhibition of cell migration and proliferation induced by BAY W 6228 (80% decrease) was completely prevented by the addition of mevalonate and partially prevented (60-80%) by farnesol and geranylgeraniol, confirming the specific role of isoprenoid metabolites-probably through a prenylated protein(s)-in regulating these cellular events. The present results provide evidence that BAY W 6228 interferes, at least in vivo, with smooth muscle cells migration and proliferation, major processes involved in atherogenesis.
AB - The major relation existing between cell growth, migration and cholesterol homeostasis prompted us to investigate the effect of the new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin (BAY W 6228) on these cellular events. The molecule inhibited in a dose-dependent manner the migration and the replication (evaluated as cell number and nuclear incorporation of 3H-thymidine) of rat arterial SMC with IC50 values of 2.7 μM and 0.5 μM, respectively. Among the tested statins BAY W 6228 resulted to be the most potent inhibitor of cholesterol synthesis and cell proliferation. Conditions producing 80-90% inhibition of cholesterol synthesis correlate with approximately 50% inhibition of cell growth. Similar results were obtained in SMC from human femoral artery. The in vitro inhibition of cell migration and proliferation induced by BAY W 6228 (80% decrease) was completely prevented by the addition of mevalonate and partially prevented (60-80%) by farnesol and geranylgeraniol, confirming the specific role of isoprenoid metabolites-probably through a prenylated protein(s)-in regulating these cellular events. The present results provide evidence that BAY W 6228 interferes, at least in vivo, with smooth muscle cells migration and proliferation, major processes involved in atherogenesis.
KW - BAY W 6228
KW - Cerivastatin
KW - Isoprenoids
KW - Myocyte migration
KW - Myocyte proliferation
KW - Statins
UR - http://www.scopus.com/inward/record.url?scp=0029980255&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029980255&partnerID=8YFLogxK
U2 - 10.1006/phrs.1996.0009
DO - 10.1006/phrs.1996.0009
M3 - Article
C2 - 8817647
AN - SCOPUS:0029980255
VL - 33
SP - 55
EP - 61
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
IS - 1
ER -