pyrophosphate and pitavastatin

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.. 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 micromol/L) but inhibited them at high concentration (1 micromol/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 micromol/L) of pitavastatin reduced fibroblast growth factor-2-induced angiogenesis, whereas low concentration (0.3 micromol/L) tended to increase angiogenesis.. Pitavastatin has a biphasic effect on HMVECs and on angiogenesis through at least 2 different pathways that include the mevalonate pathway.

Topics: Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Diphosphates; Dose-Response Relationship, Drug; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Microcirculation; Neovascularization, Physiologic; Quinolines; Skin