Pitavastatin alters the expression of thrombotic and fibrinolytic proteins in human vascular cells

Markle, Ronald A.; Han, Jihong; Summers, Barbara D.; Yokoyama, T.; Hajjar, Katherine A.; Hajjar, David P.; Gotto, Antonio M.; Nicholson, Andrew C.

doi:10.1002/jcb.10602

Cited by 50 publications

(41 citation statements)

References 45 publications

(62 reference statements)

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“…Therefore, we believe our histological data regarding the pleiotropic effects of statin therapy on ISR tissues in humans are valuable. Several studies showing that statins have anti-thrombotic effects independent of lipidlowering action [32][33][34] may support our data.…”

Section: Discussionsupporting

confidence: 89%

Preprocedural Statin Administration can Reduce Thrombotic Reaction After Stent Implantation

Nishino

Hoshida²,

Kato

et al. 2008

Circ J

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Section: Discussionsupporting

confidence: 89%

Preprocedural Statin Administration can Reduce Thrombotic Reaction After Stent Implantation

Nishino

Hoshida²,

Kato

et al. 2008

Circ J

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“…Statins blunt induction of tissue factor expression induced by inflammatory mediators, 7,8,29,30 but the impact of statins on basal TF expression is less clear. We examined the effect of atorvastatin and sterol restriction on the level of TF antigen and its cofactor activity with fVIIa in EA.hy926 cells ( Figure 3).…”

Section: Statin Treatment and Sterol Restriction Reduce Fviia/tf Actimentioning

confidence: 99%

Inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG CoA) Reductase Blunts Factor VIIa/Tissue Factor and Prothrombinase Activities via Effects on Membrane Phosphatidylserine

Dietzen

Page

Tetzloff

et al. 2007

ATVB

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Objective-3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) exhibit antithrombotic properties that are independent of reductions in circulating LDL cholesterol. We hypothesized that these antithrombotic properties are mediated by membrane alterations secondary to disrupted lipid metabolism. Methods and Results-EA.hy926 cells were incubated in the presence of 1 mol/L atorvastatin supplemented with fetal bovine serum or lipid-depleted serum mixtures. Lipid restriction alone had no effect on cell lipid composition but when atorvastatin was included, phosphatidylserine, sphingomyelin, and cholesterol were reduced by 50% while ceramide content decreased by 70%. These changes in lipid composition did not alter the association of decay accelerating factor or tissue factor with lipid rafts. Atorvastatin in combination with lipid restriction reduced factor VIIa/tissue factor activity by as much as 75% but did not alter tissue factor expression. Prothrombinase activity was reduced to an extent similar to factor VIIa/tissue factor. Mevalonic acid but not LDL reversed the observed changes in lipid content and prothrombinase activity induced by atorvastatin. These findings were confirmed in primary cells. Conclusions-Inhibition

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“…29 There are some reports of its pleiotropic effects on ECs; pitavastatin increased thrombomodulin, tissue-type plasminogen activator and nitric oxide production, and decreased plasminogen activator inhibitor 1 and inflammatory cytokine. [31][32][33][34] Moreover, pitavastatin has augmented capillary formation in the ischemic limb of an animal model. 35 These pleiotropic effects of pitavastatin are similar to those of conventional statins and so it is interesting to know whether or not the effect of pitavastatin on the migration, proliferation, and apoptosis of ECs, as well as on angiogenesis, is as good as that of conventional statins.…”

mentioning

confidence: 99%

Biphasic Effect of HMG-CoA Reductase Inhibitor, Pitavastatin, on Vascular Endothelial Cells and Angiogenesis

Katsumoto

Shingu

Kuwashima

et al. 2005

Circ J

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tatins reduce the serum cholesterol level by inhibiting 3-hydroxyl-3-methyl coenzyme A (HMG-CoA) reductase. Mega-trials have demonstrated the safety and efficiency of long-term cholesterol-lowering therapy using low-dose statin, 1 and that intervention with statins prevent cardio-and cerebrovascular events in patients with hypercholesterolemia. [2][3][4][5][6] It has been suggested that the preventive effect of statins is attributable to their cholesterol-lowering action, but there is research demonstrating that statin therapy also prevents cardiovascular events in patients with an average cholesterol level, 4 suggesting that statins prevent coronary vascular events not only through cholesterol-lowering but also through some other process. The mechanisms of these effects beyond the reduction of cholesterol, the so-called pleiotropic functions, have been gradually elucidated by a number of studies.The pleiotropic functions of statins are involved in the regulation of cell adhesion molecules and the cell cycle, 7-11 inhibition of cell growth and/or induction of apoptosis in vascular smooth muscle cells, [12][13][14] 16,17 and inhibition of vascular NAD(P)H oxidase, 18 among others. Moreover, we have reported that in experiments in dogs cerivastatin inhibited migration of ECs in vitro and intimal thickening of balloon-injured arteries in vivo. 19 With respect to angiogenesis, some researchers have show that simvastatin and cerivastatin promote collateral vessel formation in ischemic tissues of animal models. 20,21 On the other hand, these same drugs reportedly inhibited the migration and viability of ECs, and interrupted angiogenesis. [22][23][24] More recent reports indicate that simvastatin, cerivastatin and atorvastatin exert a biphasic effect on cultured ECs and angiogenesis in a dose-dependent manner. [25][26][27] "New generation" statins, which have a stronger effect on cholesterol reduction than conventional statins, have been developed and one of them, pitavastatin, exhibits a potent hypolipidemic effect in both animal and human trials. [28][29][30] At a dose of 4 mg/day pitavastatin has been shown to be equivalent to atorvastatin at a dose of 80 mg/day in reducing low-density lipoprotein in heterozygous familial hypercholesterolemia patients. 29 There are some reports of its pleiotropic effects on ECs; pitavastatin increased thrombomodulin, tissue-type plasminogen activator and nitric oxide production, and decreased plasminogen activator inhibitor 1 and inflammatory cytokine. [31][32][33][34] Moreover, pitavastatin has augmented capillary formation in the ischemic limb of an animal model. 35 These pleiotropic effects of pitavastatin are similar to those of conventional statins and so it is interesting to know whether or not the effect of pitavastatin on the migration, proliferation, and Methods and ResultsThe effects of pitavastatin on the migration, proliferation and viability of human epidermal microvessel endothelial cells (HMVECs) were examined using scratch assay, chemotaxis chamber, bromodeoxyuridin...

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Pitavastatin alters the expression of thrombotic and fibrinolytic proteins in human vascular cells

Cited by 50 publications

References 45 publications

Preprocedural Statin Administration can Reduce Thrombotic Reaction After Stent Implantation

Preprocedural Statin Administration can Reduce Thrombotic Reaction After Stent Implantation

Inhibition of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG CoA) Reductase Blunts Factor VIIa/Tissue Factor and Prothrombinase Activities via Effects on Membrane Phosphatidylserine

Biphasic Effect of HMG-CoA Reductase Inhibitor, Pitavastatin, on Vascular Endothelial Cells and Angiogenesis

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