Atorvastatin reverses the dysfunction of human umbilical vein endothelial cells induced by angiotensin II

Abstract

Statins exert pleiotropic effects on endothelial cells, in addition to lowering cholesterol. This study evaluated angiotensin II (Ang II)-induced dysfunction in human umbilical vein endothelial cells (HUVECs), and the effects of atorvastatin (Ator) on induced HUVECs in vitro. The cytotoxicity of Ang II and Ator was determined by the MTT assay. A series of cellular responses were screened, including oxidative stress, cellular apoptosis, inflammatory response, autophagy, expression of endothelial nitric oxide synthase and the angiogenic function of HUVECs. Ator returned these cellular responses to a normal level. The present study also examined cellular organelle dysfunction. In HUVECs, Ang II triggered mitochondrial damage, as demonstrated by a decreased mitochondrial membrane potential, while Ator attenuated this Ang II-induced damage. The observed cellular dysfunction may cause endothelial senescence due to excessive cell injury. The current study examined several aging markers, which revealed that these disorders of cellular functions triggered endothelial senescence, which was delayed by Ator. Ator also suppressed Ang II-induced angiogenesis damage. The data presented in this study strongly suggested that Ang II induced a series of processes that lead to cellular dysfunction in HUVECs, including oxidative stress, inflammation, and mitochondrial damage, leading to apoptosis and endothelial senescence. However, Ator significantly reversed these effects and modulated intracellular stability. The present study indicated that Ator serves an antagonistic role against HUVEC dysfunction and may potentially prevent several diseases, including coronary disease and atherosclerosis, by maintaining cellular homeostasis.

Atorvastatin disrupts primary human brain microvascular endothelial cell functions via prenylation‐dependent mitochondrial inhibition and oxidative stress

“…Although the primary uses of atorvastatin and other statins are for the treatment of dyslipidemia, the beneficial effects in the cardiovascular system may go beyond the cholesterol‐lowering effects to target other cholesterol‐independent effects, such as improving endothelial functions and attenuating vascular remodelling [7,20,21]. Atorvastatin has been reported to reverse the dysfunction of human umbilical vein endothelial cells induced by angiotensin II [21]. Interestingly, studies also show that atorvastatin induces endothelial dysfunctions via inhibition of endothelium tube formation and migration [10,22].…”

Atorvastatin and Conditioned Media from Atorvastatin-Treated Human Hematopoietic Stem/Progenitor-Derived Cells Show Proangiogenic Activity In Vitro but Not In Vivo

“…Interestingly, 1 μ mol/L atorvastatin enhanced VEGF and IL8 promoter activities but decreased their production by human microvascular endothelial cells in hypoxia [31]. Furthermore, Dang and coworkers showed that 10 μ mol/L atorvastatin did not affect tube formation by HUVEC in an overnight stimulation [32]. Atorvastatin also decreased endothelial senescence and dysfunction induced by angiotensin II [32].…”

“…Furthermore, Dang and coworkers showed that 10 μ mol/L atorvastatin did not affect tube formation by HUVEC in an overnight stimulation [32]. Atorvastatin also decreased endothelial senescence and dysfunction induced by angiotensin II [32]. On the other hand, atorvastatin administered orally inhibited inflammatory angiogenesis and production of VEGF in sponge transplants in mice [33].…”

The microRNA in ventricular remodeling: the miR-30 family

“…Ang II induces cardiomyocyte hypertrophy, heart damage, and fibrosis [73]. Dang et al’s [74] data suggest that Ang II also causes oxidative stress, inflammation, and mitochondrial damage, which leads to apoptosis and endothelial senescence. The binding of Ang II to the AT1 receptor can cause apoptosis of cardiomyocytes, resulting in a series of complex reaction processes such as decreased Bcl-2/Bax and caspase-3 activation [75].…”