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

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 concentrations alleviates H2O2-induced oxidative stress and damage and at high concentrations inhibits prenylation. Our work provides better understanding on the multiple differential effects and the underlying mechanisms of pravastatin on HMVEC-C, which may be of relevance to the influence of statins in cardiovascular system.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Hu K,Wan Q

doi

10.1016/j.bbrc.2019.02.090

subject

Has Abstract

pub_date

2019-04-02 00:00:00

pages

476-481

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)30286-4

journal_volume

511

pub_type

杂志文章

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