Effects of various doses of atorvastatin on vascular endothelial cell apoptosis and autophagy in�vitro

Abstract

Atorvastatin (Lipitor™) is a lipid-lowering agent that is widely used in the treatment of cardiovascular diseases. Previous research has largely focused on its cholesterol-lowering effects; however, a limited number of studies have investigated the actions of atorvastatin on vascular endothelial cells. In the present study, the effects of various doses of atorvastatin were investigated on human umbilical vein endothelial cells (HUVECs). HUVECs were treated with various concentrations of atorvastatin in serum-free or serum-containing medium, and alterations in HUVEC morphology were observed. Cell survival and necrosis rates were evaluated using sulforhodamine B and lactate dehydrogenase assays, respectively. In addition, the protein expression levels of cellular apoptosis and autophagy markers were detected using western blot analysis. The results revealed that HUVEC morphology was altered following treatment with various concentrations of atorvastatin. In addition, autophagy was demonstrated to be induced by atorvastatin treatment at all concentrations, whereas high concentrations appeared to induce apoptosis and suppress the survival of HUVECs. In conclusion, the results of the present study suggested that various doses of atorvastatin may exert differential effects on HUVECs, and high doses may suppress angiogenesis. Therefore, atorvastatin may present a novel potential anti-tumor therapeutic strategy. However, further studies are required to fully elucidate the association between the dose of atorvastatin and its clinical outcome.

A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol

“…Zhao et al . (2019) [ 12 ] report that atorvastatin had a dose-dependent effect on HUVEC apoptosis. Although no such effect was observed at a concentration of 0.7 μM (391 ng/mL), it was found that cell viability was decreased and necrosis increased at 7, 35 and 70 μM (3910, 19 551 and 39 102 ng/mL).…”

Role of autophagy in regulating interleukin‐10 and the responses to corticosteroids and statins in asthma

“…The effect of statins on macrophage autophagy in asthma has also not been reported, although statins have been shown to induce autophagy‐mediated retardation of macrophage‐driven atherosclerotic plaque progression and to reduce Mycobacterium tuberculosis burden 35‐37 . However, statins are able to both induce and inhibit excessive autophagy resulting in different cellular outcomes, depending on the cell type, disease condition and drug concentration 38,39 . We have demonstrated that anti‐autophagy effects of ICS and statins in asthma with the additive enhancement, which was exhibited in sputum macrophages.…”

Atorvastatin and pravastatin stimulate nitric oxide and reactive oxygen species generation, affect mitochondrial network architecture and elevate nicotinamide N‐methyltransferase level in endothelial cells

“…Thus, we have chosen 5-μM concentration according to the rule of 'the mildest effective treatment.' This concentration was also recommended in the vast majority of publications (Demyanets et al, 2006;Godoy et al, 2019;Zhao et al, 2019). Moreover, under such conditions, no symptoms of reduced viability were observed (these preliminary data are not shown here).…”

“…In both cases, 1‐μM concentration was too low while 5‐μM statins efficiently increased ICAM‐1 protein content, and further increase of their concentration did not elevate this effect. Thus, we have chosen 5‐μM concentration according to the rule of ‘the mildest effective treatment.’ This concentration was also recommended in the vast majority of publications (Demyanets et al, 2006; Godoy et al, 2019; Zhao et al, 2019). Moreover, under such conditions, no symptoms of reduced viability were observed (these preliminary data are not shown here).…”