Department of anesthesiology and Intensive Care Medicine, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.
Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, 40530, Sweden.
Sci Rep. 2017 Dec 12;7(1):17434. doi: 10.1038/s41598-017-16363-9.
Sepsis induced cardiac dysfunction (SIC) is a severe complication to sepsis which significantly worsens patient outcomes. It is known that bacteria have the capacity to release outer membrane vesicles (OMVs), which are nano-sized bilayered vesicles composed of lipids and proteins, that can induce a fatal inflammatory response. The aim of this study was to determine whether OMVs from a uropathogenic Escherichia coli strain can induce cardiac dysfunction, and to elucidate any mechanisms involved. OMVs induced irregular Ca oscillations with a decreased frequency in cardiomyocytes through recordings of intracellular Ca dynamics. Mice were intraperitoneally injected with bacteria-free OMVs, which resulted in increased concentration of pro-inflammatory cytokine levels in blood. Cytokines were increased in heart lysates, and OMVs could be detected in the heart after OMVs injection. Troponin T was significantly increased in blood, and echocardiography showed increased heart wall thickness as well as increased heart rate. This study shows that E. coli OMVs induce cardiac injury in vitro and in vivo, in the absence of bacteria, and may be a causative microbial signal in SIC. The role of OMVs in clinical disease warrant further studies, as bacterial OMVs in addition to live bacteria may be good therapeutic targets to control sepsis.
脓毒症相关性心功能障碍（SIC）是脓毒症的一种严重并发症，显著恶化了患者的预后。已知细菌具有释放外膜囊泡（OMVs）的能力，OMVs 是由脂质和蛋白质组成的纳米双层囊泡，可引发致命的炎症反应。本研究旨在确定来自尿路致病性大肠杆菌菌株的 OMV 是否可诱导心功能障碍，并阐明涉及的任何机制。通过记录细胞内 Ca 动力学，发现 OMVs 诱导心肌细胞中 Ca 振荡不规则且频率降低。将无细菌的 OMVs 腹膜内注射到小鼠体内，导致血液中促炎细胞因子水平升高。心肌组织匀浆中的细胞因子增加，并且在 OMVs 注射后可在心脏中检测到 OMVs。肌钙蛋白 T 在血液中显著增加，超声心动图显示心壁厚度增加以及心率增加。本研究表明，在不存在细菌的情况下，大肠杆菌 OMVs 可在体外和体内诱导心脏损伤，并且可能是 SIC 中的一种致病微生物信号。OMVs 在临床疾病中的作用值得进一步研究，因为除了活细菌之外，细菌 OMVs 可能是控制脓毒症的良好治疗靶标。
