Atorvastatin improves the cardiac function of rats after acute myocardial infarction through ERK1/2 pathway
Authors: Z-L Liu
Z-X Zhang
H-T Zeng
M Zhao
S-M Zhong
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Atorvastatin; extracellular signal-regulated kinase (ERK) 1/2 pathway; acute myocardial infarction (AMI); cardiac function; Sprague-Dawley (SD) rats
Affiliations: Department of Pharmacy, Shenzhen Longgang E.N.T. Hospital, Shenzhen, China. .

Abstract:  Objective: To study the regulatory effect of atorvastatin (ATV) on the extracellular signal-regulated kinase (ERK) 1/2 pathway and explore its effect on acute myocardial infarction (AMI) rats. Materials and methods: The rat model of AMI was established, and the model rats were randomly divided into AMI group and ATV-AMI group, and Sham group was also set up. At 4 weeks after successful modeling, the cardiac function indexes of Sprague-Dawley (SD) rats were detected via magnetic resonance imaging (MRI) and echocardiography (ECG). After the rats were executed, the left ventricular weight index (LVWI) was measured, and the myocardial damage was detected via hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, the messenger ribonucleic acid (mRNA) expressions of collagen I and collagen III in myocardial tissues were detected via Real Time-Polymerase Chain Reaction (PCR), and the expressions of ERK1/2 pathway-related proteins in myocardial tissues were detected via Western blotting. Results: After administration of ATV for AMI, the fractional shortening (FS%) and ejection fraction (EF%) were significantly restored. Compared with that in ATV-AMI group, LVWI was significantly increased in AMI group (p&lt;0.05), indicating that ATV could improve the cardiac function after AMI. The results of HE staining and TUNEL staining showed that ATV-AMI group had slighter myocardial damage and significantly lower apoptosis rate than AMI group, indicating that ATV could reverse AMI through the ERK1/2 pathway. Besides, the mRNA expressions of collagen I and collagen III were higher in AMI group and ATV-AMI group than those in Sham group (p&lt;0.05), while they were significantly lower in ATV-AMI group than those in AMI group (p&lt;0.05). The expressions of ERK1/2 pathway-related proteins were also higher in AMI group and ATV-AMI group than those in Sham group (p&lt;0.05). Conclusions: ATV can significantly improve the cardiac function of SD rats after AMI, whose mechanism is related to the expression of the ERK1/2 pathway. 

Retracted: No

PubPeer comments:
 Figure 3.  HE staining of rat s heart. A, Sham group, B, AMI group, C, ATV-AMI group. The myocardial morphology is normal in Sham group, and the myocardial damage caused by AMI is reversed in ATV-AMI group (magnification  Compare with Figure 3 from [Shi et al (2019)] ,  Pathological changes in myocardial tissues of rats in each group detected via HE staining ...  ...and with Fig 2 from [Fan et al (2019)] :  HE staining of heart. A, MALAT1 group (u00d710). B, siMALAT1 group (u00d710).  Red boxes indicate further overlaps for those other papers. , 
  Figure 4. Apoptosis level detected via TUNEL staining, A, Sham group, B, ATV-AMI group, C, AMI group. Apoptosis occurs in a large number of myocardial cells in AMI group, while it is significantly reduced in ATV-AMI group .   ATV-AMI and (part of)  Sham also appear in Fig 4 of [Zhu et al (2020)] , as ATO and Control...  ...and as Figure 3 from [Wang, Cheng Jiang (2020)] , as Control and Model.  , 
 Fig 3 again:  Compare with Figure 2 from [Xu et al (2019)] .  Pathological changes in rat myocardial tissues. Myocardial cells were arranged in order in the normal group (A), while was disorderly arranged in the SHR group (B), with thickened muscle fibers and myocardial fibrosis .  , 
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