miR-339-3p promotes AT1-AA-induced vascular inflammation by upregulating NFATc3 protein expression in vascular smooth muscle cells  

作　　者：Yang Li Yaolin Long Xiaoyan Zhi Haihu Hao Xiaohui Wang Huirong Liu Li Wang 

机构地区：[1]School of Basic Medical Sciences,Shanxi Medical University,Taiyuan 030001,China [2]Department of Orthopedics,Shanxi Bethune Hospital&Shanxi Academy of Medical Sciences,Taiyuan 030032,China [3]School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第2期295-303,共9页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Sciences Foundation of China(No.31871177);the Cultivate Scientific Research Excellence Programs of Higher Education Institutions in Shanxi(No.2020KJ034);the Basic Research Project of Shanxi Science and Technology Department(No.202103021224347);the Natural Science Foundation of Shanxi Province Applied Basic Research Program(No.201901D111197);the Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease and the Shanxi“1331 Project”Key Subjects Construction.

摘　　要：Vascular inflammation induced by angiotensin II-1 receptor autoantibody(AT1-AA)is involved in the occurrence and development of various cardiovascular diseases.miR-339-3p is closely related to the degree of vasodilation of aortic aneurysm and is also involved in the occurrence and development of acute pancreatitis.However,it is still unclear whether miR-339-3p influences AT1-AA-induced vascular inflammation.In this study,the role and mechanism of miR-339-3p in AT1-AA-induced vascular inflammation are studied.RT-PCR detection shows that the miR-339-3p levels in the thoracic aorta and serum exosomes of AT1-AA-positive rats are significantly increased.The miRwalk database predicts the mRNAs that miR-339-3p can bind to their 5′UTR.Subsequently,it is found that the number of genes contained in the T cell receptor pathway is high through KEGG analysis,and NFATc3 among them can promote the secretion of various inflammatory cytokines.AT1-AA-induced upregulation of miR-339-3p expression in vascular smooth muscle cells(VSMCs)can lead to a significant increase in NFATc3 protein level and promote vascular inflammation.Inhibition of miR-339-3p with antagomir-339-3p can significantly reverse AT1-AA-induced high expressions of IL-6,IL-1βand TNF-αproteins in rat thoracic aorta and VSMCs.That is,AT1-AA can upregulate the expression of miR-339-3p in VSMCs,and the increased miR-339-3p targets the 5′UTR of NFATc3 mRNA to increase the protein level of NFATc3,thereby aggravating the occurrence of vascular inflammation.These findings provide new experimental evidence for the involvement of miRNAs in regulating vascular inflammatory diseases.

关 键 词：angiotensin II-1 receptor autoantibody(AT1-AA) miR-339-3p NFATc3 vascular inflammation 

分 类 号：R543[医药卫生—心血管疾病]