Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a criti...Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a critical role in the development of heart diseases.Therefore,we hypothesized that anti-ferroptosis agent might be a novel potential therapeutic strategy for sepsis-induced cardiac injury.Herein,we demonstrated that a small biocompatible and MRI-visible melanin nanoparticles(MMPP)improves myocardial function by inhibiting ROS-related ferroptosis signaling pathway.In LPS-induced murine sepsis model,after a single dose intravenously injection of MMPP treatment,MMPP markedly alleviated the myocardial injury including cardiac function and heart structure disorder through suppressing iron-accumulation induced ferroptosis.In vitro,MMPP inhibited cardiomyocyte death by attenuating oxidative stress,inflammation and maintaining mitochondrial homeostasis.Collectively,our findings demonstrated that MMPP protected heart against sepsis-induced myocardial injury via inhibiting ferroptosis and inflammation,which might be a novel therapeutic approach in future.展开更多
基金supported by grants of the National Natural Science Foundation of China to YS(82272221,32071263),ZQ(81971887,82172170)and CL(82202403)the Tianjin Natural Science Foundation to ZQ(20JCYBJC01260,20JCYBJC01230)+3 种基金the Key Laboratory of Emergency and Trauma(Hainan Medical University),Ministry of Education to YS(KLET-202018)the Fundamental Research Funds for the Central Universities,Nankai University to ZQ(63211140)the Scientific Research Project of Tianjin Education Commission to CL(2020KJ206)National College Students’Innovative Entrepreneurial Training Plan Program to RL(202210062001).
文摘Myocardial injury as one of the severe complications leads to the increasing morbidity and mortality in patients with sepsis.Recent studies reported that reactive oxygen species(ROS)-mediated ferroptosis plays a critical role in the development of heart diseases.Therefore,we hypothesized that anti-ferroptosis agent might be a novel potential therapeutic strategy for sepsis-induced cardiac injury.Herein,we demonstrated that a small biocompatible and MRI-visible melanin nanoparticles(MMPP)improves myocardial function by inhibiting ROS-related ferroptosis signaling pathway.In LPS-induced murine sepsis model,after a single dose intravenously injection of MMPP treatment,MMPP markedly alleviated the myocardial injury including cardiac function and heart structure disorder through suppressing iron-accumulation induced ferroptosis.In vitro,MMPP inhibited cardiomyocyte death by attenuating oxidative stress,inflammation and maintaining mitochondrial homeostasis.Collectively,our findings demonstrated that MMPP protected heart against sepsis-induced myocardial injury via inhibiting ferroptosis and inflammation,which might be a novel therapeutic approach in future.
