Effect of atorvastatin on pulmonary hypertension rats through regulating notch signaling pathway
Authors: J-Y Liu
Y-T Zhu
X-Q Zhang
H Liu
G-Q Cao
M-M Tang
Journal: European review for medical and pharmacological sciences (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Atorvastatin; pulmonary hypertension; Notch signaling pathway; rats; RVSP
Affiliations: Internal Medicine, Jinan Tianqiao People's Hospital, Jinan, China. .

Abstract:  Objective: To study the effect of atorvastatin on pulmonary hypertension (PAH) rats through regulating the Notch signaling pathway. Materials and methods: The rat model of PAH was established via hypoxic feeding and the Control group (n=10), PAH model group (Model group, n=10) and atorvastatin treatment group (ATO group, n=10) were set up. The right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined, the wet/dry weight (W/D) ratio of lung tissues was determined, and the tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) and interleukin-6 (IL-6) were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining and the apoptosis level was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Finally, the Notch signaling pathway and apoptosis level in tissues were detected via quantitative Polymerase Chain Reaction (qPCR), and the protein expression level of Notch pathway in lung tissues was determined through Western blotting. Results: Both RVSP and RVHI in Model group were significantly higher than those in Control group and ATO group (p&lt;0.05). In Model group, the levels of inflammatory factors MPO, IL-6, and TNF-α were significantly increased, and the W/D ratio was also significantly increased compared with those in Control group (p&lt;0.05). The results of HE staining showed that the lung tissue injury in Model group was severe (p&lt;0.05). According to the TUNEL staining results, the number of apoptotic cells in lung tissues was markedly larger in Model group than that in ATO group (p&lt;0.05), and the expression levels of Caspase-3 and IL-6 in Model group were remarkably higher than those in ATO group (p&lt;0.05), while the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was remarkably lower than that in ATO group (p&lt;0.05). Besides, the gene and protein expression levels of Notch1 in ATO group were evidently lower than those in Model group (p&lt;0.05), indicating that atorvastatin can effectively suppress the expression of Notch. Conclusions: Atorvastatin can inhibit PAH in rats by suppressing the Notch pathway. 

Retracted: No

PubPeer comments:
 Figure 3:  HE staining. The lung tissue injury is remarkably alleviated in ATO group. A, Control group (20u00d7), B, Model group (20u00d7), and C, ATO group . ![file] Compare with Figure 2 from [Wang, Cheng Jiang (2019)] .  Pathological changes in lung tissues of each group detected via HE staining (magnification u00d7 10). Lung tissue injury is significantly alleviated in Ator group. ![file] , 
 Fig 4,  Apoptosis level of lung tissues in each group detected via TUNEL staining (magnification: 20u00d7). The number of TUNEL-positive cells in Model group is remarkably larger than that in Control group . ![file] Please compare with Figure 3 from Wang, Cheng Jiang.  Apoptosis level of lung tissues in each group detected via TUNEL staining (magnification: 200u00d7). The number of TUNEL-positive cells in lung tissues in Ator group is remarkably larger than that of Model group . ![file] , 
 #1 I should have seen this earlier. Figure 2 from Wang, Cheng Jiang (2019). ![file] , 
 Fig 4 again: ![] Compare Control panel with Normal panel of Fig 1 from [Lun et al (2020)] . ![file] , 
 Fig 4 again: ![] Compare Control panel with Normal panel of Fig 1 from [Lun et al (2020)] . ![file] , 
 Fig 4 again: ![file] Figure 4 of [Zeng et al (2019)] .  Apoptosis level detected via TUNEL staining, A, Sham group, B, ATV-AMI group, C, AMI group . ![file] , 
 Because these papers all have at least one image in common, while not sharing any authors or affiliations, they appear to be produced by a paper mill, which might have supplied the papers and the figures. As of today, this set contains at least 9 papers, all connected to each other with at least one photo, as per the work of Hoya Camphorifolia. * H. Wang et al. - DOI: 10.26355 eurrev_201912_19695 - https: pubpeer.com publications 7BB185FB656F0F8214F92EDFE047FF * HT Zeng et al. - DOI: 10.26355 eurrev_201908_18757 - https: pubpeer.com publications B226E56465DACEA93791215756340B * MH Lun et al. - DOI: 10.26355 eurrev_202005_21366 - https: pubpeer.com publications AAA8F559D37A6D853CC16764A06A53 * Q Xu et al. - DOI: 10.26355 eurrev_201909_19026 - https: pubpeer.com publications C6F5DA3CA8F64BD57CE8A9B38616D0 * YJ Shi et al. - DOI: 10.26355 eurrev_201906_18082 - https: pubpeer.com publications 153695342827B732C15C614F61DF10 * YJ Wan et al. - DOI: 10.26355 eurrev_201908_18622 - https: pubpeer.com publications 41C0C61998A1A6C6339689A61A6ABF * YT Zhu et al. - DOI: 10.26355 eurrev_202005_21205 - https: pubpeer.com publications 277C24C645B71AF55A72A1200C46B4 * YY Wang et al. - DOI: 10.26355 eurrev_201912_19696 - https: pubpeer.com publications 702E90DEA6ED9278B2F67828C5329D * YZ Fan et al. - DOI: 10.26355 eurrev_201910_19306 - https: pubpeer.com publications 0B80BCE778E3D360504102D662CDE5 , 
 #7 Thanks a lot, WE are going to investigate the problem your found. , 
 #11 Please do share how your investigation proceeds. It would be educational to hear how the papermill responds. , 
 Thanks a lot, WE are going to investigate the problem your found. , 
 Fig 3 again: ![file] Figure 2 from Wang, Cheng Jiang (2019). ![] Another sighting! Fig 1 from  Influence of miRNA-30a-5p on Pulmonary Fibrosis in Mice with Streptococcus pneumoniae Infection through Regulation of Autophagy by Beclin-1 ([Liu et al 2021] ). ![file] ,