Therapeutic silencing miR-146b-5p improves cardiac remodeling in a porcine model of myocardial infarction by modulating the wound reparative phenotype

作     者：Yiteng Liao Hao Li Hao Cao Yun Dong Lei Gao Zhongmin Liu Junbo Ge Hongming Zhu Yiteng Liao;Hao Li;Hao Cao;Yun Dong;Lei Gao;Zhongmin Liu;Junbo Ge;Hongming Zhu

作者机构：Research Center for Translational MedicineShanghai East HospitalTongji University School of MedicineShanghai 200120China Department of CardiologyShanghai Tenth People's HospitalTongji University School of MedicineShanghai 200072China Department of Cardiovascular SurgeryShanghai East HospitalTongji University School of MedicineShanghai 200120China Department of Ultrasound in MedicineShanghai East HospitalTongji University School of MedicineShanghai 200120China Department of CardiologyShanghai Institute of Cardiovascular DiseasesZhongshan Hospital of Fudan UniversityShanghai 200032China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2021年第12卷第3期

页      面：194-212页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：CMVEC CTO, (IL-6) 

主　　题：cardiac fibrosis microRNA porcine model myocardial infarction 

摘      要：Fibrotic remodeling is an adverse consequence of immune response-driven phenotypic modulation of cardiac cells following myocardial infarction(Ml).MicroRNA-146b(miR-146b)is an active regulator of immunomodulation,but its function in the cardiac inflammatory cascade and its clinical implication in fibrotic remodeling following Ml remain largely ***,miR-146b-5p was found to be upregulated in the infarcted myocardium of mice and the serum of myocardial ischemia ***-and loss-of-function experiments demonstrated that miR-146b-5p was a hypoxia-induced regulator that governed the pro-fibrotic phenotype transition of cardiac *** of miR-146b-5p activated fibroblast proliferation,migration,and fibroblast-to-myofibroblast transition,impaired endothelial cell function and stress survival,and disturbed macrophage paracrine ***,the opposite effects were observed when miR-146b-5p expression was *** assays and rescue studies demonstrated that the miR-146b-5p target genes mediating the above phenotypic modulations included interleukin 1 receptor associated kinase 1(IRAKI)and carcinoembryonic antigen related cell adhesion molecule 1(CEACAM1).Local delivery of a miR-146b-5p antagomir significantly reduced fibrosis and cell death,and upregulated capillary and reparative macrophages in the infarcted myocardium to restore cardiac remodeling and function in both mouse and porcine Ml *** inhibition of miR-146b-5p may represent a novel therapeutic approach to treat cardiac fibrotic remodeling and dysfunction following Ml.