Exosomes secreted from cardiomyocytes suppress the sensitivity of tumor ferroptosis in ischemic heart failure

作     者：Ye Yuan Zhongting Mei Zhezhe Qu Guanghui Li Shuting Yu Yingqi Liu Kuiwu Liu Zhihua Shen Jiaying Pu Yanquan Wang Changhao Wang Zhiyong Sun Qian Liu Xiaochen Pang Ao Wang Zijing Ren Tong Wang Ying Liu Jinhuan Hong Jiajie Xie Xin Li Zhonghua Wang Weijie Du Baofeng Yang Ye Yuan;Zhongting Mei;Zhezhe Qu;Guanghui Li;Shuting Yu;Yingqi Liu;Kuiwu Liu;Zhihua Shen;Jiaying Pu;Yanquan Wang;Changhao Wang;Zhiyong Sun;Qian Liu;Xiaochen Pang;Ao Wang;Zijing Ren;Tong Wang;Ying Liu;Jinhuan Hong;Jiajie Xie;Xin Li;Zhonghua Wang;Weijie Du;Baofeng Yang

作者机构：Department of Pharmacology(The State-Province Key Laboratories of Biomedicine Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbinChina Department of Pharmacy(The University Key Laboratory of Drug ResearchHeilongjiang Province)The Second Affiliated Hospital of Harbin Medical UniversityHarbinChina Research Unit of Noninfectious Chronic Diseases in Frigid ZoneChinese Academy of Medical Sciences2019RU070 HarbinChina Department of Clinical PharmacologyCollege of PharmacyHarbin Medical UniversityHarbinChina Department of CardiologyThe First Affiliated Hospital of Harbin Medical UniversityHarbinChina Translational Medicine Research and Cooperation Center of Northern ChinaHeilongjiang Academy of Medical SciencesHarbinChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2023年第8卷第4期

页      面：2007-2021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：the National Natural Science Fund of China(U21A20339,82273928,82273026) CAMS Innovation Fund for Medical Sciences(CIFMS)2019-I2M-5-078 Outstanding Youth Project of Natural Science Fund of Heilongjiang Province(YQ2020H010,YQ2020H019) Heilongjiang Innovative Talent Training Fund for Young Teachers(to Ye Yuan in 2020) College of Pharmacy,Harbin Medical University,Excellent Young Talents Funding(2019-YQ-13) 

主　　题：Exosomes enriched prevailing 

摘      要：Heart failure(HF)patients in general have a higher risk of developing *** animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect relationship between these two disease *** ferroptosis,a prevailing form of non-apoptotic cell death,has been considered a promising therapeutic strategy for human *** critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine ***,whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been ***,we demonstrate that myocardial infarction(MI)decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft ***-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis *** expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as *** of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in ***-enriched miR-22-3p was packaged in exosomes and transferred into tumor *** of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ***4,a pro-ferroptotic gene,was experimentally established as a target of miR-22-3p in tumor *** together,our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from ***