Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Experimental Investigation
Biphasic Effect of HMG-CoA Reductase Inhibitor, Pitavastatin, on Vascular Endothelial Cells and Angiogenesis
Masayuki KatsumotoTetsuji ShinguRieko KuwashimaAtsunori NakataShuichi NomuraKazuaki Chayama
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2005 Volume 69 Issue 12 Pages 1547-1555

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Abstract

Background HMG-CoA reductase inhibitors (statins) have pleiotropic effects beyond their cholesterol-lowering effect. However, consensus on the effect of statins on endothelial cells and angiogenesis has not yet been reached. Methods and Results The effects of pitavastatin on the migration, proliferation and viability of human epidermal microvessel endothelial cells (HMVECs) were examined using scratch assay, chemotaxis chamber, bromodeoxyuridine incorporation, trypan blue dye exclusion test, and nuclear DNA staining. Pitavastatin enhanced the migration, proliferation and viability of HMVECs at a low concentration (0.01 μmol/L) but inhibited them at high concentration (1 μmol/L). The inhibitory effect on cell viability by high concentration of pitavastatin was recovered by geranylgeranyl pyrophosphate, but the effect on migration and proliferation was not. The cell activating effect of a low concentration of pitavastatin was reversed by both farnesyl pyrophosphate and geranylgeranyl pyrophosphate. A quail chorioallantoic membrane assay showed that high concentration (1 μmol/L) of pitavastatin reduced fibroblast growth factor-2-induced angiogenesis, whereas low concentration (0.3 μmol/L) tended to increase angiogenesis. Conclusion Pitavastatin has a biphasic effect on HMVECs and on angiogenesis through at least 2 different pathways that include the mevalonate pathway. (Circ J 2005; 69: 1547 - 1555)

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© 2005 THE JAPANESE CIRCULATION SOCIETY
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