Biphasic influence of pravastatin on human cardiac microvascular endothelial cell functions under pathological and physiological conditions

Biochemical and Biophysical Research Communications
Kun Hu, Qian Wan

Abstract

HMG-CoA reductase inhibitor statins are used to treat patients with hypercholesterolemia. The pleiotropic effects of statins have been recently extended to the regulation of angiogenesis. However, the observations on the effects of statins on endothelial cells seem to be contradictory. In this work, we systematically analysed the effects of pravastatin at concentrations covering 10,000-fold range on the functions of human cardiac microvascular endothelial cells (HMVEC-C) under H2O2-induced oxidative stress and normal physiological conditions. We observed the biphasic effects of pravastatin in protecting HMVEC-C dysfunctions induced by H2O2: pravastatin at low concentrations significantly enhanced vascular network formation, growth, migration and survival under H2O2-induced oxidative stress condition whereas this effect disappeared at higher concentrations. Interestingly, pravastatin at low concentrations did not affect HMVEC-C functions but at high concentrations significantly inhibited HMVEC-C vascular network formation, growth, migration and survival in a dose-dependent manner. We further demonstrated the different molecular mechanisms of the action of pravastatin at low and high concentrations on HMVEC-C: pravastatin at low ...Continue Reading

Citations

Jan 10, 2021·Journal of Clinical Medicine·Nadia MeyerFrauke von Versen-Höynck
Jul 31, 2021·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Zhi LiYan Gong

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