Atorvastatin protects cardiomyocytes from oxidative stress by inhibiting LOX-1 expression and cardiomyocyte apoptosis
Authors: Ling Shen
Jianhua Zhu
Li Zhang
Qiqi Wang
Zhigang Wu
Linfang Cheng
Lei Zhang
Dongchen Zhou
Journal: Acta biochimica et biophysica Sinica (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Akt; H2O2, lectin-like oxidized low-density lipoprotein receptor-1; apoptosis; atorvastatin; cardiomyocyte.
Affiliations: Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China ., State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou 31003, China., Department of Cardiology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 31003, China.

Abstract:  Coronary artery disease (CAD) is a major health problem worldwide. The most severe form of CAD is acute coronary syndrome (ACS). Recent studies have demonstrated the beneficial role of atorvastatin in ACS; however, the mechanisms underlying this effect have not been fully clarified. Growing evidence indicates that activation of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in oxidative stress-induced cardiomyocyte apoptosis during ACS. In this study, we examined whether atorvastatin inhibits H2O2-induced LOX-1 expression and H9c2 cardiomyocyte apoptosis, and investigated the underlying signaling pathway. Treatment of H9c2 cardiomyocytes with H2O2 resulted in elevated expression of LOX-1 mRNA and protein, as well as increased caspase-3 and -9 protein expression and cell apoptosis. H2O2-induced LOX-1 expression, caspase protein expression, and cardiomyocyte apoptosis were attenuated by pretreatment with atorvastatin. Atorvastatin activated H2O2-inhibited phosphorylation of Akt in a concentration-dependent manner. The Akt inhibitor, LY294002, inhibited the effect of atorvastatin on inducing Akt phosphorylation and on suppressing H2O2-mediated caspase up-regulation and cell apoptosis. These findings indicate that atorvastatin protects cardiomyocyte from oxidative stress via inhibition of LOX-1 expression and apoptosis, and that activation of H2O2-inhibited phosphorylation of Akt may play an important role in the protective function of atorvastatin. 

Retracted: No

PubPeer comments:
 Figure 3D appears to include 2 images which overlap. Note: Previous correction is regarding author affiliations. u201cThe original article [1] contained incorrect affiliations for the authors. The original article has now been updated to reflect the correct affiliations.u201d *** ![file] , 
 Thank you for bringing this to our attention. After having checked the manuscript and the raw data, we found that the mentioned image has indeed been mismatched during the preparation of this panel in these two control groups. We apologize for this unintentional mistake and thank for your concern again. Please see below for the corrected panel d of figure 3. We emphasize that this figure replacement does not affect the validity of the data and conclusions drawn, or any other aspect of the published paper. We have already contacted the journal office to issue a correction. This comment is valuable and very helpful for improving our paper, as well as the important guiding significance to our research. Warm regards , 
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 Figure 3 appears to have more problems, and an overlap with figure 7: ![file] ![file] , 
 More with figure 6: ![file] , 
 #3 1) Could the author comment on the status if the original issue? It has been 7 months since the authors first contacted the journal. 2) Is the journal aware of the subsequent concerns? , 
 Any further response would be nice ... in particular as there is even more overlap for example in figure 6 a ![file] ![file] , 
 Thank you for bringing the comments to our attention. After checking the manuscript and the raw data carefully immediately, we found the errors and contacted the journal office and the chief-editor in the first time at February 05, 2020. Probably due to the emergence of nCoV-19, we haven t gotten a reply from the editor, we then tried to keep contacting the journal at June 03, 2020 and August 11, 2020. Finally we got the reply until recently at August 16, 2020. We have written the correction letter and contacted the journal to put a statement to the errors as soon as possible. The images were indeed mismatched because of our careless and problems in editing software during the preparation of the pictures. We apologize for the unintentional mistakes and thank for your concern again. We emphasize that the images replacement do not affect the validity of the data and conclusions drawn. These comments are valuable and very helpful for improving our paper, as well as the important guiding significance to our research. Warm regards. , 
 #8 Dr. Dong: Good news. I heard back from the Editor in Charge of Journal of Hematology Oncology who said they will investigate. Hopefully the corresponding author will hear from them soon. , 
 Retraction, 22 October 2020: https: jhoonline.biomedcentral.com articles 10.1186 s13045-020-00969-0  In accordance with the guidelines published by COPE, the authors have retracted this article [1] because of significant concerns regarding a number of Figures presented in this work. In Fig. 3C and 3D there are duplications in the NC and NC-LV groups in the H460 cells, NC-LV, OE-miR-330-3p-LV and anti-miR-330-3p-LV groups in the H1975 cells. In Fig. 7D, the H1975 NC-LV Vec image has been duplicated from the H460 NC image in Fig. 3C. There are multiple duplications throughout Fig. 6, and there are duplications in Fig. 9D (OE-miR-330-3p-LV and OE-miR-330-3p-LVu2009+u2009U0126 groups in the H460 cells, OE-miR-330-3p-LV group in the H1975 cells). The data reported in this article are therefore unreliable. All authors agree to this retraction. ,