Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibitors; comparison with other human cell types

Nègre-Aminou, Pascale; Vliet, Arlène K. van; Erck, Monique van; Thiel, Gerald; Leeuwen, R.E.W. van; Cohen, Louis

doi:10.1016/s0005-2760(96)00184-1

Cited by 195 publications

(112 citation statements)

References 32 publications

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“…In a similar study using¯uvastatin sodium, another HMGCoA reductase, while the per cent areas of smooth muscle cells, collagen ®bres, and extracellular lipid deposits were decreased, the per cent area of macrophages was increased in the early atherosclerotic lesions of young WHHL rabbits (Shiomi et al, 1998). Both cerivastatin and¯uvastatin show inhibitory e ects on proliferation of smooth muscle cells in in vitro studies (Corsini et al, 1996;Negre-Aminou et al, 1997;Bellosta et al, 1998) and in vivo studies using normocholesterolaemic rabbits which had neointimal thickening of arteries caused by injury (Soma et al, 1993;Bandoh et al, 1996;Igarashi et al, 1997b). However, in our studies using young WHHL rabbits, uvastatin caused a decrease in the per cent area of smooth muscle cells in the atherosclerotic lesions whereas cerivastatin did not, despite the similar hypolipidemic e ects of the two drugs.…”

Section: Discussionmentioning

confidence: 44%

“…On the other hand, in vitro studies (Negre-Aminou et al, 1997;Corsini et al, 1996;Igarashi et al, 1997b) and an in vivo study using balloon-injured arteries of normocholesterolaemic rabbits (Igarashi et al, 1997a,b) showed that cerivastatin inhibited proliferation of smooth muscle cells. Regarding the disagreement on inhibition of smooth muscle cell proliferation between our present results and previous reports, we think that the mechanism regulating smooth muscle cell proliferation in spontaneously developed atherosclerosis may be di erent from those in injured arteries or culture conditions, and cerivastatin may e ectively inhibit smooth muscle cell proliferation in culture conditions or injured arteries.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, cerivastatin did not a ect the blood pressure and heart rate in dogs or the hematological parameters of rats (Dr H. Bischo , Bayer AG, Germany, personal communication). On the other hand, in vitro studies demonstrated that although pravastatin has a weak e ect on inhibition of smooth muscle cell growth, cerivastatin caused a potent inhibition of proliferation of human smooth muscle cells (Negre-Aminou et al, 1997;Corsini et al, 1996). Igarashi et al (1997a,b) also reported that cerivastatin suppressed neointimal thickening by attenuating intimal smooth muscle cell proliferation and in®ltration of macrophages in balloon-injured rabbit models.…”

Section: Introductionmentioning

confidence: 99%

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Effect of cerivastatin sodium, a new inhibitor of HMG‐CoA reductase, on plasma lipid levels, progression of atherosclerosis, and the lesional composition in the plaques of WHHL rabbits

Shiomi

Ito

1999

British J Pharmacology

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1 The aim of this study was to examine whether cerivastatin sodium, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a ects the lesional composition of spontaneously developed atherosclerosis due to hypercholesterolaemia and delays progression of the lesions. 2 We administered cerivastatin to 2-month-old WHHL rabbits, a low-density lipoprotein receptorde®cient animal model, at a dose of 0.6 mg kg 71 day 71 for 32 weeks. We examined the plasma lipid levels, the severity of atherosclerosis, and composition of atherosclerotic lesions. Lesional composition was determined using immunohistostaining for macrophages and smooth muscle cells, and Azan-Mallory staining for collagen ®bres and extracellular lipid deposits. 3 Compared to the control group, the plasma cholesterol levels were decreased in the treated group by 39% (12.7+0.6 mmol L 71 versus 20.9+1.0 mmol L 71 , P50.001). Atherosclerosis was suppressed by about 37% as measured by the thickness of the aortic lesions (158+13 mm versus 250+15 mm, P50.001), and by 28% as measured by coronary stenosis (62.7+11.4 versus 86.9+12.2, P50.05). In the cerivastatin group, regarding the per cent areas of lesional components in the lesion area, the macrophages (21.0+1.5% versus 27.9+1.9%, P50.01) and extracellular lipid deposits (3.2+0.4% versus 5.1+0.4%, P50.001) were decreased in the aortic lesions, and the per cent area of macrophages in the coronary lesions was also decreased (4.9+1.4% versus, 11.6+2.4%, P50.05). The per cent area of smooth muscle cells and collagen ®bres did not signi®cantly decrease. 4 These results indicate that cerivastatin contributed to the plaque stabilization and delayed progression of early atherosclerosis in young WHHL rabbits, in addition to the potent hypolipidemic e ects.

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Section: Discussionmentioning

confidence: 44%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of cerivastatin sodium, a new inhibitor of HMG‐CoA reductase, on plasma lipid levels, progression of atherosclerosis, and the lesional composition in the plaques of WHHL rabbits

Shiomi

Ito

1999

British J Pharmacology

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“…One explanation for this finding may be that because statins are known to inhibit cell proliferation, nonconfluent monolayers were not able to reach confluence in the presence of simvastatin. 23 Furthermore, in vascular smooth muscle cells, statins are known to induce apoptosis at high concentration. 21 Taken together, these findings suggest that care has to be taken to use statins when endothelial cells are in a proliferative state, eg, in wound healing.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Improves Disturbed Endothelial Barrier Function

et al. 2000

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Background-Recent clinical trials have established that inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) reduce the risk of acute coronary events. These effects of statins cannot be fully explained by their lipid-lowering potential. Improved endothelial function may contribute to the positive effects of statin treatment. Methods and Results-In the present study, we report that simvastatin reduces endothelial barrier dysfunction, which is associated with the development of atherosclerosis. Treatment of human umbilical vein endothelial cells for 24 hours with 5 mol/L simvastatin reduced the thrombin-induced endothelial barrier dysfunction in vitro by 55Ϯ3%, as assessed by the passage of peroxidase through human umbilical vein endothelial cell monolayers. Similar effects were found on the thrombin-induced passage of 125 I-LDL through human aortic endothelial cell monolayers. This reduction in barrier dysfunction by simvastatin was both dose and time dependent and was accompanied by a reduction in the thrombin-induced formation of stress fibers and focal adhesions and membrane association of RhoA. Simvastatin treatment had no effect on intracellular cAMP levels. In Watanabe heritable hyperlipidemic rabbits, treatment for 1 month with 15 mg/kg simvastatin reduced vascular leakage in both the thoracic and abdominal part of the aorta, as evidenced by the Evans blue dye exclusion test. The decreased permeability was not accompanied by a reduction of oil red O-stainable atherosclerotic lesions. Conclusions-These data show that simvastatin, in a relatively high concentration, improves disturbed endothelial barrier function both in vitro and in vivo. The data also support the beneficial effects of simvastatin in acute coronary events by mechanisms other than its lipid-lowering effect.

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“…Numerous papers have reported that the frequency of coronary heart disease is significantly decreased by statin administration (26)(27)(28). In addition to the LDL-C lowering effect, other pleiotropic effects of statins have also been demonstrated (12,29,30).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of MMP-9 Activity in THP-1 Cells by 7-ketocholesterol and Its Suppression by the HMG-CoA Reductase Inhibitor Fluvastatin

Ozaki

Miyashita

Watanabe

et al. 2005

JAT

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We investigated the effect of 7-ketocholesterol (7-KCHO) on the activity of matrix metalloproteinase (MMP-9) in human monocytic THP-1 cells, and the inhibition of this effect by fluvastatin. In cells incubated with 7-KCHO or cholesterol, the activity of MMP-9 was enhanced, accompanying an increase in the secretion of MMP-9 proenzyme (pro-MMP-9). However, the activity of MMP-9 and the amount of pro-MMP-9 were significantly greater following incubation with 7-KCHO than cholesterol.

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Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibitors; comparison with other human cell types

Cited by 195 publications

References 32 publications

Effect of cerivastatin sodium, a new inhibitor of HMG‐CoA reductase, on plasma lipid levels, progression of atherosclerosis, and the lesional composition in the plaques of WHHL rabbits

Effect of cerivastatin sodium, a new inhibitor of HMG‐CoA reductase, on plasma lipid levels, progression of atherosclerosis, and the lesional composition in the plaques of WHHL rabbits

Simvastatin Improves Disturbed Endothelial Barrier Function

Enhancement of MMP-9 Activity in THP-1 Cells by 7-ketocholesterol and Its Suppression by the HMG-CoA Reductase Inhibitor Fluvastatin

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