Background : Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH. Methods : Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart cath-eterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline-i nduced PH (MCT- PH) male rats were treated with 17β- estradiol (E 2 ) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA. Results : Many circulating miRNAs, including miR- 21- 5p and miR- 574- 5p, were mark-edly expressed in patients and of interest in predicting mean pulmonary arterial pres-sure elevation in patients. The expression of miR- 21- 5p in the lungs was significantly upregulated in MCT- PH rats compared with the controls. However, miR- 574- 5p showed no difference in the lungs of MCT- PH rats and controls. miR- 21- 5p was se-lected for further analysis in rats as E 2 strongly regulated it. E 2 decreased miR- 21- 5p expression in the lungs of MCT- PH rats by ERβ. E 2 reversed miR- 21- 5p target gene FilGAP downregulation in the lungs of MCT- PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c- Jun in the lungs of MCT- PH rats was inhibited by E 2 and miR- 21- 5p antagonist. Conclusions : miR- 21- 5p level was remarkably associated with PH severity in patients. Moreover, the miR- 21- 5p/FilGAP signaling pathway modulated the protective effect of E 2 on MCT- PH through ERβ.

Xiaoyi Hu;Qian Wang;Hui Zhao;Wenhui Wu;Qinhua Zhao;Rong Jiang;Jinming Liu;Lan Wang;Ping Yuan

Department of Cardio-Pulmonary Circulation,Shanghai Pulmonary Hospital,School of Medicine,Tongji University, Shanghai 200433,China;Institute of Bismuth Science,University of Shanghai for Science and Technology,Shanghai,China

动物模型与实验医学（英文）

[1]Xiaoyi Hu;Qian Wang;Hui Zhao;Wenhui Wu;Qinhua Zhao;Rong Jiang;Jinming Liu;Lan Wang;Ping Yuan-.Role of miR - 21- 5p/ FilGAP axis in estradiol alleviating the progression of monocrotaline- induced pulmonary hypertension)[J].动物模型与实验医学（英文）,2022(03):217-226

FilGAP,eterization,Monocrotaline,nduced,Subgroups

Role,5p,axis,estradiol,alleviating,progression,monocrotaline,induced,pulmonary,hypertension,Background,Aberrant,expression,microRNAs,miRNAs,has,been,associated,pathogenesis,PH,It,however,not,clear,whether,involved,estrogen,rescue,Methods,Fresh,plasma,samples,were,prepared,from,idiopathic,arterial,IPAH,patients,healthy,controls,undergoing,right,heart,cath,Shanghai,Pulmonary,Hospital,From,each,total,was,tagged,hybridized,microarray,chips,MCT,male,rats,vehicle,cotreated,receptor,ER,antagonist,Results,Many,circulating,including,edly,expressed,interest,predicting,mean,sure,elevation,lungs,significantly,upregulated,compared,However,showed,difference,lected,further,analysis,strongly,decreased,by,reversed,target,downregulation,abnormal,RhoA,ROCK2,Rac1,Jun,inhibited,Conclusions,level,remarkably,severity,Moreover,signaling,pathway,modulated,protective,effect,through

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