PINK1 contained in huMSC-derived exosomes prevents cardiomyocyte mitochondrial calcium overload in sepsis via recovery of mitochondrial Ca2+ efflux

作者：Qin Zhou, Min Xie, Jing Zhu, Qin Yi, Bin Tan, Yasha Li, Liang Ye, Xinyuan Zhang, Ying Zhang, Jie Tian, Hao Xu · 发表于：Stem Cell Research & Therapy · 年份：2021 · DOI：10.1186/s13287-021-02325-6 · 被引用次数：73 · 研究领域：Extracellular vesicles in disease、Cardiac Ischemia and Reperfusion、Cardiac Fibrosis and Remodeling

Abstract Background Sepsis is a systemic inflammatory response to a local severe infection that may lead to multiple organ failure and death. Previous studies have shown that 40–50% of patients with sepsis have diverse myocardial injuries and 70 to 90% mortality rates compared to 20% mortality in patients with sepsis without myocardial injury. Therefore, uncovering the mechanism of sepsis-induced myocardial injury and finding a target-based treatment are immensely important. Objective The present study elucidated the mechanism of sepsis-induced myocardial injury and examined the value of human umbilical cord mesenchymal stem cells (huMSCs) for protecting cardiac function in sepsis. Methods We used cecal ligation and puncture (CLP) to induce sepsis in mice and detect myocardial injury and cardiac function using serological markers and echocardiography. Cardiomyocyte apoptosis and heart tissue ultrastructure were detected using TdT-mediated dUTP Nick-End Labeling (TUNEL) and transmission electron microscopy (TEM), respectively. Fura-2 AM was used to monitor Ca 2+ uptake and efflux in mitochondria. FQ-PCR and Western blotting detected expression of mitochondrial Ca 2+ distribution regulators and PTEN-induced putative kinase 1 (PINK1). JC-1 was used to detect the mitochondrial membrane potential (Δψm) of cardiomyocytes. Results We found that expression of PINK1 decreased in mouse hearts during sepsis, which caused cardiomyocyte mitochondrial Ca 2+ efflux disorder, mitochondrial c...