Effect of atorvastatin on pulmonary arterial hypertension in rats through PI3K/AKT signaling pathway
Authors: H Jiang
X-D Cheng
Y-Y Wang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: atorvastatin; pulmonary arterial hypertension; PAH; rats; phosphatidylinositol 3-hydroxy kinase
Affiliations: Neonatal Intensive Care Unit, Affiliated Hospital of Jining Medical College, Jining, China. .

Abstract:  Objective: The aim of this study was to investigate the effect of atorvastatin on pulmonary arterial hypertension (PAH) in rats and to observe its specific regulatory mechanism through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. Materials and methods: The model of PAH was successfully established in rats via hypoxia feeding. All rats were divided into three groups, including Control group (n=15), PAH model group (Model group, n=15) and atorvastatin treatment group (Ator group, n=15). Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) were detected via enzyme-linked immunosorbent assay (ELISA). Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined as well. Meanwhile, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining. Furthermore, the apoptosis level of lung tissues in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. In addition, the expression levels of PI3K/AKT signaling pathway and apoptotic genes in lung tissues were detected via quantitative Polymerase Chain Reaction (qPCR). Results: In Model group, the levels of TNF-α and IL-6 increased significantly, while the level of NO decreased. Both RVSP and RVHI in Model group were significantly higher than those of Control group and Ator group (p&lt;0.05). The results of HE staining revealed that Model group showed significantly severe lung tissue injury (p&lt;0.05). According to the results of TUNEL staining, the number of apoptotic cells in lung tissues in Model group was significantly smaller than that of Ator group (p&lt;0.05). Meanwhile, the expression level of cysteinyl aspartate-specific proteinase-3 (Caspase-3) in Model group was markedly lower than that of Ator group (p&lt;0.05). However, the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was markedly higher than that of Ator group (p&lt;0.05). In Ator group, the expression levels of PI3K and AKT in lung tissues were remarkably higher than those of Model group (p&lt;0.05). All the above results indicated that atorvastatin could effectively up-regulate the expressions of PI3K and AKT (p&lt;0.05). Conclusions: Atorvastatin regulates the symptoms of PAH in rats through activating the PI3K/AKT signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 2.  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] Compare with Figure 3 from [Zhu et al (2020)] :  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] , 
 Figure 3.  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] Please compare with Fig 4 from Zhu et al.,  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] , 
 #1 I should have seen this earlier. Figure 2. ![file] , 
 Fig 3 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 , 
 #1 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] ,