2P 0577 Effects of atorvastatin on plasm
166
2P-0576
Tuesday September 30, 2003: Poster Session
Therapy
Pitavastatin inhibits atherosclerosis induced by chronic
inhibition of nitric oxide synthesis in moderate
hypercholesterolemic rabbits via inhibiting macrophage
accumulation and macrophage foam cell formation
M. Kitahara 1 , T. Tamaki 2 , Y. Saito 3 . 1 Biological Research Laboratories,
Nissan Chemical Industries Ltd., Saitama; 2 Tokyo Research Laboratories,
Kowa Company Ltd.; 3 The Second Department of Internal Medicine, School
of Medicine, Chiba University, Japan
Objective: To elucidate the effect of statin on atherosclerosis in moderate hypercholesterolemia and inflammatory responses in atherosclerosis, we studied
the effect of pitavastatin on chronic nitric oxide synthase(NOS) inhibitionaccelerated atherosclerosis in rabbits, monocyte-endothelial cell adhesion,
macrophage foam cell formation and cholesterol efflux from macrophages.
Methods: After 1 week preconditioning with low dose L(w)-nitro arginine methyl ester(L-NAME), rabbits were fed 0.2% cholesterol and 0.175%
L-NAME containing diet and orally administered with pitavastatin(0.1 or 0.3
mg/kg/day) for 8 weeks. THP-1 cells and human umbilical vein endothelial
cells(HUVEC) were treated with statins for 48 hrs, and THP-1 cells were
loaded on HUVEC for 2 hrs. RAW264.7 cells were treated with statins for
26 hrs and incubated with acetylated LDL or oxidized LDL for 3 days and
cholesterol ester was measured. In cholesterol efflux assay, RAW264.7 cells
were labeled with 14 C-cholesterol and incubated with statins for 30 hrs.
Results: Pitavastatin suppressed the surface atherosclerotic lesion area of
the aorta and intimal thickening(intima/media ratio), RAM11 anti-macrophage
antibody positive area and Oil red O stained area of the aortic arch. Pitavastatin potently inhibited cholesterol ester accumulation in RAW264.7 cells and
THP-1 cell adhesion to HUVEC. These inhibitory effects of pitavastatin were
attenuated by mevalonate. Atorvastatin suppressed cholesterol efflux from
RAW264.7 cells but pitavastatin did not.
Conclusion: Pitavastatin suppressed chronic inhibition of NOS-accelerated
development of atherosclerosis with suppression of macrophage and lipid
accumulation via inhibiting monocytes-endothelial cell adhesion and macrophage foam cell formation in moderate hypercholesterolemic rabbits.
2P-0577
Effects of atorvastatin on plasma fibrinogen, plasminogen
activator inhibitor-1 (PAI-1) and serum homocysteine in
patients with familial hypercholesterolaemia (FH) and
non-familial hypercholesterolaemia (NFH)
T. Rahman, S. Muid, N.S. Osman, K. Yusoff, H. Nawawi. Faculty of
Medicine, Universiti Kebangsaan Malaysia, Malaysia
Objective: To determine the effects of atorvastatin on plasma fibrinogen,
plasminogen activator inhibitor-1(PAI-1) and serum homocysteine (Hcys)
levels in patients with Familial Hypercholesterolaemia(FH) and non-Familial
Hypercholesterolaemia(NFH).
Materials and Methods: 113 patients (47 FH and 66 NFH, 59 males,
54 females, mean±SD age=45.3±years) and 40 age and gender matched normolipaemic controls were recruited. FH patients were treated with 80mg/day
atorvastatin (FHs) and NFH patients were either given 10mg/day atorvastatin
(NFHs) or placebo (NFHp). Fasting blood samples were analysed for lipid profile, fibrinogen, PAI-1 and Hcys at baseline, 2 weeks, 3 months and 9 months.
Results: At baseline, the Hcys levels of FHs and NFHs were higher than
controls (mean D: 9.4±2.9 vs 10.5±3.6 vs 7.8±2.4 µmol/L, p
2P-0576
Tuesday September 30, 2003: Poster Session
Therapy
Pitavastatin inhibits atherosclerosis induced by chronic
inhibition of nitric oxide synthesis in moderate
hypercholesterolemic rabbits via inhibiting macrophage
accumulation and macrophage foam cell formation
M. Kitahara 1 , T. Tamaki 2 , Y. Saito 3 . 1 Biological Research Laboratories,
Nissan Chemical Industries Ltd., Saitama; 2 Tokyo Research Laboratories,
Kowa Company Ltd.; 3 The Second Department of Internal Medicine, School
of Medicine, Chiba University, Japan
Objective: To elucidate the effect of statin on atherosclerosis in moderate hypercholesterolemia and inflammatory responses in atherosclerosis, we studied
the effect of pitavastatin on chronic nitric oxide synthase(NOS) inhibitionaccelerated atherosclerosis in rabbits, monocyte-endothelial cell adhesion,
macrophage foam cell formation and cholesterol efflux from macrophages.
Methods: After 1 week preconditioning with low dose L(w)-nitro arginine methyl ester(L-NAME), rabbits were fed 0.2% cholesterol and 0.175%
L-NAME containing diet and orally administered with pitavastatin(0.1 or 0.3
mg/kg/day) for 8 weeks. THP-1 cells and human umbilical vein endothelial
cells(HUVEC) were treated with statins for 48 hrs, and THP-1 cells were
loaded on HUVEC for 2 hrs. RAW264.7 cells were treated with statins for
26 hrs and incubated with acetylated LDL or oxidized LDL for 3 days and
cholesterol ester was measured. In cholesterol efflux assay, RAW264.7 cells
were labeled with 14 C-cholesterol and incubated with statins for 30 hrs.
Results: Pitavastatin suppressed the surface atherosclerotic lesion area of
the aorta and intimal thickening(intima/media ratio), RAM11 anti-macrophage
antibody positive area and Oil red O stained area of the aortic arch. Pitavastatin potently inhibited cholesterol ester accumulation in RAW264.7 cells and
THP-1 cell adhesion to HUVEC. These inhibitory effects of pitavastatin were
attenuated by mevalonate. Atorvastatin suppressed cholesterol efflux from
RAW264.7 cells but pitavastatin did not.
Conclusion: Pitavastatin suppressed chronic inhibition of NOS-accelerated
development of atherosclerosis with suppression of macrophage and lipid
accumulation via inhibiting monocytes-endothelial cell adhesion and macrophage foam cell formation in moderate hypercholesterolemic rabbits.
2P-0577
Effects of atorvastatin on plasma fibrinogen, plasminogen
activator inhibitor-1 (PAI-1) and serum homocysteine in
patients with familial hypercholesterolaemia (FH) and
non-familial hypercholesterolaemia (NFH)
T. Rahman, S. Muid, N.S. Osman, K. Yusoff, H. Nawawi. Faculty of
Medicine, Universiti Kebangsaan Malaysia, Malaysia
Objective: To determine the effects of atorvastatin on plasma fibrinogen,
plasminogen activator inhibitor-1(PAI-1) and serum homocysteine (Hcys)
levels in patients with Familial Hypercholesterolaemia(FH) and non-Familial
Hypercholesterolaemia(NFH).
Materials and Methods: 113 patients (47 FH and 66 NFH, 59 males,
54 females, mean±SD age=45.3±years) and 40 age and gender matched normolipaemic controls were recruited. FH patients were treated with 80mg/day
atorvastatin (FHs) and NFH patients were either given 10mg/day atorvastatin
(NFHs) or placebo (NFHp). Fasting blood samples were analysed for lipid profile, fibrinogen, PAI-1 and Hcys at baseline, 2 weeks, 3 months and 9 months.
Results: At baseline, the Hcys levels of FHs and NFHs were higher than
controls (mean D: 9.4±2.9 vs 10.5±3.6 vs 7.8±2.4 µmol/L, p