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Beneficial vasoactive endothelial effects of fluvastatin: focus on prostacyclin and nitric oxide

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Abstract

Statins are believed to exert beneficial effects against cardiovascular disease beyond correction of dyslipidemia. There are however still very sparse data on how individual statins interact with the production of vasoactive eicosanoids and nitric oxide (NO) in human vascular endothelial cells. Here we have determined how fluvastatin affects the mRNA expression of genes associated with vascular reactivity as well as the formation of two major vasodilators, prostacyclin (PGI2) and NO, in human endothelial cells. Also, the influence of fluvastatin on arterial resistance was assessed in isolated small arteries. We show that the promoter activity of prostacyclin synthase (PTGIS), the mRNA expression of PTGIS and endothelial nitric oxide synthase (eNOS), and the production of PGI2 and NO are significantly induced by fluvastatin. Also, strong rapid dilatation ex vivo was observed, with the equal contribution of PGI2 and NO. Our findings in cell culture experiments and in isolated human arteries indicate that fluvastatin-evoked endothelium-derived vasodilator production may confer protection of the endothelial cells via both acute and long-term effects of fluvastatin treatment. If these effects take place in vivo, we suggest a protective pleiotropic role of fluvastatin on the cardiovascular system, particularly at the level of the vascular endothelium, to ameliorate the process of atherogenesis and in the acute manner to reduce vascular tone.

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Acknowledgments

This work was supported by AstraZeneca and the Swedish Science Council (Medicine 04496 to A.R.) and funds from the Karolinska Institutet.

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Authors and Affiliations

  1. Division of Clinical Pharmacology C1:68, Department of Laboratory Medicine, Karolinska University Hospital, 141 86, Stockholm, Sweden

    Cristine Skogastierna, Erik Eliasson, Anders Rane & Lena Ekström

  2. Division of Obstetrics and Gynaecology, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital, 141 86, Stockholm, Sweden

    Leonid Luksha & Karolina Kublickiene

Authors
  1. Cristine Skogastierna
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  2. Leonid Luksha
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  3. Karolina Kublickiene
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  6. Lena Ekström
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Correspondence to Cristine Skogastierna.

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Skogastierna, C., Luksha, L., Kublickiene, K. et al. Beneficial vasoactive endothelial effects of fluvastatin: focus on prostacyclin and nitric oxide. Heart Vessels 26, 628–636 (2011). https://doi.org/10.1007/s00380-010-0097-x

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  • DOI: https://doi.org/10.1007/s00380-010-0097-x

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