Atorvastatin attenuates homocysteine-induced apoptosis in human umbilical vein endothelial cells via inhibiting NADPH oxidase-related oxidative stress-triggered p38MAPK signaling

Bao, Xiaomei; Wu, Chunfang; Li, Guoping

doi:10.1038/aps.2009.135

Cited by 31 publications

(27 citation statements)

References 29 publications

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“…Recently, clinical study has indicated that atorvastatin decreases circulating CXCL12, an angiogenic chemokine, in patients with coronary artery disease, congestive heart failure, and (or) myocardial infarction, without affecting the plasma lipid profile (Camnitz et al 2012). Atorvastatin showed anti-senescence and anti-apoptotic actions in human umbilical vein endothelial cells (HUVECs) exposed to oxidative stress (Bao et al 2009;Ota et al 2010). Thus, atorvastatin protects endothelial cells and has restorative pleiotropic effects.…”

Section: Introductionmentioning

confidence: 98%

Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats

ChaudagarKiranj

MehtaAnita

2014

Can. J. Physiol. Pharmacol.

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Atorvastatin, a lipid lowering agent, possesses various pleiotropic vasculoprotective effects, but its role in coronary angiogenesis is still controversial. Our objective was to study the effects of atorvastatin on the angiogenic responsiveness of coronary endothelial cells (cEC) from normal and diabetic rats. Male Wistar rats were distributed among 9 groups; (i) normal rats, (ii) 30 day diabetic rats, (iii) 60 day diabetic rats, (iv) normal rats administered a low dose of atorvastatin (1 mg/kg body mass, per oral (p.o.), for 15 days); (v) 30 day diabetic rats administered a low dose of atorvastatin; (vi) 60 day diabetic rats administered a low dose of atorvastatin; (vii) normal rats administered a high dose of atorvastatin (5 mg/kg, p.o., for 15 days); (viii) 30 day diabetic rats administered a high dose of atorvastatin; (ix) 60 day diabetic rats administered a high dose of atorvastatin. Each group was further divided into 2 subgroups, (i) sham ischemia-reperfusion and (ii) rats hearts that underwent ischemia-reperfusion. Angiogenic responsiveness the and nitric oxide (NO) releasing properties of the subgroups of cECs were studied using a chorioallantoic membrane assay and the Griess method, respectively. Atorvastatin treatment significantly increased VEGF-induced angiogenic responsiveness and the NO-releasing properties of cECs from all of the subgroups, compared with their respective non-treated subgroups except for the late-phase diabetic rat hearts that underwent ischemia-reperfusion, and the high dose of atorvastatin treatment groups. These effects of atorvastatin were significantly inhibited by pretreatment of cECs with l-NAME, wortmannin, and chelerythrine. Thus, treatment with a low dose of atorvastatin improves the angiogenic responsiveness of the cECs from normal and diabetic rats, in the presence of VEGF, via activation of eNOS-NO release.

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Section: Introductionmentioning

confidence: 98%

Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats

ChaudagarKiranj

MehtaAnita

2014

Can. J. Physiol. Pharmacol.

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“…Short-term atorvastatin treatment in patients with CAD was reported to be regenerative on the endothelium, through the inhibition of endothelial apoptosis (Schmidt-Lucke et al, 2010), even induced by hyperhomocysteinemia (Bao et al, 2009). On the other hand, high micromolar concentrations of statins, 100-to 200-fold higher than serum statin levels in patients, have been reported to induce apoptosis (Katsiki et al, 2010).…”

Section: B Statins and Endothelial Functionmentioning

confidence: 99%

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

Gazzerro

Proto²,

Gangemi³

et al. 2011

Pharmacol Rev

401

370

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“…Statins have been found to reduce oxidative stress-induced apoptosis of endothelial cells [1] and restore the survival and function of EPCs [13,18,23] . These effects may contribute to both ischemia-induced neovascularization and endothelial regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…Our previous study has found that Hcy may induce ROS accumulation and endothelial cell apoptosis in human umbilical vein endothelial cells (HUVECs) via activating NADPH oxidase-related oxidative stress and the p38MAPK signaling pathway [1] . Recent studies have suggested that endothelial progenitor cells (EPCs) may contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium [2,3] .…”

Section: Introductionmentioning

confidence: 99%

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

Bao

2010

Acta Pharmacol Sin

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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.

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Atorvastatin attenuates homocysteine-induced apoptosis in human umbilical vein endothelial cells via inhibiting NADPH oxidase-related oxidative stress-triggered p38MAPK signaling

Cited by 31 publications

References 29 publications

Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats

Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

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

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