Atorvastatin inhibits homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells

Abstract

Aim: To investigate the protective effects of atorvastatin on homocysteine (Hcy)-induced dysfunction and apoptosis in endothelial progenitor cells (EPCs) and the possible molecular mechanisms. Methods: EPCs were divided into six groups: Hcy treatment groups (0, 50, and 500 μmol/L) and atorvastatin pretreatment groups (0.1, 1, and 10 μmol/L). EPC proliferation, migration, in vitro vasculogenesis activity, and apoptosis rate were assayed by the MTT assay, modified Boyden chamber assay, in vitro vasculogenesis kit, and AnnexinV-FITC apoptosis detection kit, respectively. The level of reactive oxygen species (ROS) in cells was measured using H 2 DCF-DA as a fluorescence probe. The activity of NADPH oxidase was evaluated with lucigenin-enhanced chemiluminescence. NO in the supernatant was detected by the nitrate reductase assay. The eNOS mRNA expression and p-eNOS, p-Akt, p-p38MAPK protein expression were measured by RT-PCR and Western blotting analysis, respectively. Caspase-3 activity was determined by colorimetric assay. Results: Hcy does-dependently impaired the proliferation, migration and in vitro vasculogenesis capacity of EPCs, induced cell apoptosis, increased ROS accumulation and NADPH oxidase activation, and decreased the secretion of NO compared with the control group (P<0.05 or P<0.01). The detrimental effects of Hcy were attenuated by atorvastatin pretreatment. Furthermore, Hcy caused a significant downregulation of eNOS mRNA, p-eNOS, and p-Akt protein expression as well as an upregulation of p-p38MAPK protein expression and caspase-3 activity. These effects of Hcy on EPCs were reversed by atorvastatin in a does-dependent manner. Conclusion: Atorvastatin inhibited homocysteine-induced dysfunction and apoptosis in endothelial progenitor cells, which may be related to its effects on suppressing oxidative stress, up-regulating Akt/eNOS and down-regulating the p38MAPK/caspase-3 signaling pathway.

AMP-Activated Protein Kinase Inhibits Homocysteine-Induced Dysfunction and Apoptosis in Endothelial Progenitor Cells

“…1a and b, cellular migration and proliferation of EPCs were inhibited by incubation with 500 μmol/L Hcy for 24 h compared with the control group. The results were consistent with our previous work [18]. However, here we found these detrimental effects of Hcy on EPCs were attenuated by AICAR (0.5 and 1 mmol/L) pretreatment for 1 h (Fig.…”

“…Compared with the control, 500 μmol/L Hcy significantly increased ROS accumulation (Fig. 3a), which was consistent with our previous work [18]. Here we found that this effect could be markedly blunted by AICAR (0.5 and 1 mmol/L) (Fig.…”

S-Adenosyl Methionine Prevents Endothelial Dysfunction by Inducing Heme Oxygenase-1 in Vascular Endothelial Cells

“…However, the mechanisms responsible for this association are incompletely understood. A leading hypothesis is that homocysteine increases oxidative stress and impairs endothelial function (Bao et al, 2010). Our data showed that HFD significantly increased plasma homocysteine concentration.…”

Atorvastatin enhances endothelial cell function in posttransplant poor graft function

“…19,20 or upregulating Akt signaling. 21,38,39 We provide experimental evidence that the dysfunction of BM EPCs from subjects with PGF after allo-HSCT is related to the activation of the p38 MAPK pathway and its downstream transcription factor CREB. By contrast, no significant differences were detected in phospho-JNK, ERK, or Akt levels between subjects with PGF and GGF.…”