TY - JOUR
T1 - Action of an HMG CoA reductase inhibitor, lovastatin, on apoptosis of untransformed and ts-SV40 transformed human smooth muscle cells derived from saphenous vein
AU - Unlu, Sebnem
AU - Clunn, Gerard
AU - Schachter, M.
AU - Demoliou-Mason, Catherine
AU - Hughes, Alan D.
PY - 2001
Y1 - 2001
N2 - The effect of lovastatin, an inhibitor of 3-hydroxymethyl-3-glutaryl coenzyme A (HMG CoA) reductase, was examined on human vascular smooth muscle cells (HVSMC). Untransformed HVSMC were obtained from saphenous vein and in addition an SV-40 transformed immortalized cell line (HVTs-SM1) derived from saphenous vein smooth muscle was also used. HVTs-SM1 cell proliferation and DNA synthesis were measured, and cell cycle analysis was performed by flow cytometry. Apoptosis in both cell types was assessed by a combination of flow cytometry, terminal deoxynucleotidyl transferase (TUNEL) reagent-based immunocytochemistry, DAPI staining, and DNA agarose gel electrophoresis. Lovastatin had no effect on apoptosis of HVSMC over 96 h in serum-free conditions or after stimulation with platelet-derived growth factor (PDGF-BB), although PDGF-BB increased apoptosis in HVSMC, and this was prevented by lovastatin. In HVTs-SM1 cells lovastatin inhibited cell proliferation and DNA synthesis and induced apoptosis in a time- and concentration-dependent manner. The effects of lovastatin on cell proliferation, DNA synthesis, and apoptosis were prevented by co-incubation with mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate. Lovastatin does not induce apoptosis in saphenous vein HVSMC in culture and inhibits PDGF-BB-induced DNA synthesis and apoptosis. In contrast, in SV40 transformed immortalized HVTs-SM1 cells, lovastatin induces apoptosis and inhibits cell proliferation and DNA synthesis. The pro-apoptotic effects of lovastatin in SV40 transformed HVTs-SM1 cells may be related to the enhanced rate of proliferation or deregulation of the cell cycle in this cell line.
AB - The effect of lovastatin, an inhibitor of 3-hydroxymethyl-3-glutaryl coenzyme A (HMG CoA) reductase, was examined on human vascular smooth muscle cells (HVSMC). Untransformed HVSMC were obtained from saphenous vein and in addition an SV-40 transformed immortalized cell line (HVTs-SM1) derived from saphenous vein smooth muscle was also used. HVTs-SM1 cell proliferation and DNA synthesis were measured, and cell cycle analysis was performed by flow cytometry. Apoptosis in both cell types was assessed by a combination of flow cytometry, terminal deoxynucleotidyl transferase (TUNEL) reagent-based immunocytochemistry, DAPI staining, and DNA agarose gel electrophoresis. Lovastatin had no effect on apoptosis of HVSMC over 96 h in serum-free conditions or after stimulation with platelet-derived growth factor (PDGF-BB), although PDGF-BB increased apoptosis in HVSMC, and this was prevented by lovastatin. In HVTs-SM1 cells lovastatin inhibited cell proliferation and DNA synthesis and induced apoptosis in a time- and concentration-dependent manner. The effects of lovastatin on cell proliferation, DNA synthesis, and apoptosis were prevented by co-incubation with mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate. Lovastatin does not induce apoptosis in saphenous vein HVSMC in culture and inhibits PDGF-BB-induced DNA synthesis and apoptosis. In contrast, in SV40 transformed immortalized HVTs-SM1 cells, lovastatin induces apoptosis and inhibits cell proliferation and DNA synthesis. The pro-apoptotic effects of lovastatin in SV40 transformed HVTs-SM1 cells may be related to the enhanced rate of proliferation or deregulation of the cell cycle in this cell line.
KW - Apoptosis
KW - HMG CoA reductase
KW - Lovastatin
KW - Proliferation
KW - SV40
KW - Vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=0034927965&partnerID=8YFLogxK
U2 - 10.1097/00005344-200108000-00001
DO - 10.1097/00005344-200108000-00001
M3 - Article
C2 - 11483865
AN - SCOPUS:0034927965
SN - 0160-2446
VL - 38
SP - 161
EP - 173
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 2
ER -