MicroRNA‑1929‑3p participates in murine cytomegalovirus‑induced hypertensive vascular remodeling through Ednra/NLRP3 inflammasome activation
Authors: Zhen Huang
Yan Tang
Lamei Wang
Wei Zhou
Yongmin Liu
Yunzhong Shi
Zhengyu Zhang
Dongmei Xi
Na Tang
Hua Zhong
Jiaxin Pei
Ning Lu
Yongjia Wang
Fang He
Journal: International Journal of Molecular Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: essential hypertension; murine cytomegalovirus; vascular remodeling; miR-1929-3p; Ednra
Affiliations: Department of Pathophysiology, Key Laboratory of Education Ministry of Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University, Shihezi, Xinjiang 832002, P.R. China, Centre of Medical Functional Experiments, Medical College of Shihezi University, Shihezi, Xinjiang 832002, P.R. China, Department of Geriatrics, The First Affiliated Hospital of Medical College of Shihezi University, Shihezi, Xinjiang 832002, P.R. China, Department of Clinical Medicine, Medical College of Shihezi University, Shihezi, Xinjiang 832002, P.R. China

Abstract:  MicroRNAs (miRNAs) play an important role in the development of vascular remodeling in essential hypertension (EH) by mediating the effects of human cytomegalovirus (HCMV) on the vascular system. Therefore, the aim of the present study was to investigate the effects of murine cytomegalovirus (MCMV) infection on blood pressure and vascular function in mice, in order to elucidate the role of miR‑1929‑3p in this process. For model development, 7‑month‑old C57BL/6J mice were infected with the Smith strain of MCMV, and MCMV DNA, IgG and IgM were detected. Subsequently, blood pressure was measured via the carotid artery, and the morphological changes of the aorta were evaluated by hematoxylin and eosin and Masson's trichrome staining. miR‑1929‑3p transfection was performed using an adeno‑associated virus packaged vector and the changes in vascular structure were then observed. The levels of nitric oxide (NO) and endothelial NO synthase were also assessed with colorimetry. Vascular remodeling and expression of NLRP3 inflammasome pathway‑related proteins were detected by immunohistochemistry and western blotting. Endothelin‑1 (ET‑1), interleukin (IL)‑1β and IL‑18 were assayed by ELISA. The results revealed that MCMV infection increased the blood pressure, promoted vascular remodeling, caused endothelial cell injury, and downregulated miR‑1929‑3p. However, these effects were alleviated by miR‑1929‑3p overexpression, which downregulated endothelin A receptor (Ednra) and NLRP3 inflammasome, as well as endothelial injury‑ and vascular remodeling‑related genes. Taken together, the findings of the present study indicated that overexpression of miR‑1929‑3p may improve MCMV‑induced vascular remodeling, possibly via the deactivation of the NLRP3 inflammasome by ET‑1/Ednra. 

Retracted: No

PubPeer comments:
 Again, from this group, image recycling between two different papers. ![file] , 
 Figures 6 and 9 have recycled dot plots. ![file] ![file] , 
 Fig 11C:  (C) Images of the tumor bearing mice ![file] VII and VIII are the same image. V and VI are the same mouse, in the same dish, photographed seconds apart. More to the point, the same mice appeared in Supplementary Figure S2 of  Hyaluronic acid-grafted PLGA nanoparticles for the sustained delivery of berberine chloride for an efficient suppression of Ehrlich ascites tumors [(Bhatnagar c 2018)] , there being cured with completely different nanoparticles. ![] , 
 #2 Every cell plotted in 9A is also present in 9B. ![file] 9F and 9H differ only in the upper quadrants. ![file] , 
 #2 A few more cells are plotted in Fig 6H than in 6G, but they are certainly more similar than one would expect. ![file] , 
 #3 ![file] , 
 #4 Thanks for raising the concern regarding the similarity in the dot plot of the figure 9A and 9B. The images appear similar but not exactly the same. This may be due to the data acquisition of all the samples done at the same time with the same instrument settings, same cells, same filter, exactly the same gating, etc. , 
 #5 Regarding the similarity in the dot plot of the figure 6H and 6G, it appears that the images are similar but not exactly the same. This may be due to the data acquisition of all the samples done at the same time with the same instrument settings, same cells, same filter, exactly the same gating, etc. , 
 #6 ![] I urge you to check your records again. The mouse representing case V has the same distinguishing dye marks as the mouse for case VI; its tail is in the same posture, as if the two photos were taken a second apart. Both images show the same mouse dropping to the right of the dish, and the same marking on the dish at lower left. , 
 Here I have black white reversed 6H and superimposed it over 6G. Blue points are cells detected in the 6H data that are not present in 6G. Red points would be cells detected in 6G but not in 6H, but **there aren t any**. All the cells detected in both data runs cancel out. ![file] When 99% of cells are identical in both plots, the most parsimonious explanation is that both plots **used the same data**. Here is a similar image for Figure 9F, black-white reversed and superimposed on 9H. ![file] In the lower two quadrants, there are perhaps a dozen blue points, i.e. cells present in the 9F data and not in the 9H data. All other points cancel out because they represent cells with identical measurements in both data sets. In the upper quadrants there are some points cancelling out and also many unique to 9F. There are no cells unique to 9H, anywhere. These are unequivocally the **same data set** filtered by different gate settings. I could repeat the demonstration for 9A and 9B if anyone cares. ,