Decoding molecular signature on heart of septic mice with distinct left ventricular ejection fraction
Lina Zhang,
Desheng Qi,
Milin Peng,
Binbin Meng,
Xinrun Wang,
Xiaolei Zhang,
Zhihong Zuo,
Li Li,
Zhanwen Wang,
Wenxuan Zou,
Zhonghua Hu,
Zhaoxin Qian
Affiliations
Lina Zhang
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha, Changsha 410008, China; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha 410008, China
Desheng Qi
Department of Emergency Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
Milin Peng
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha, Changsha 410008, China; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha 410008, China
Binbin Meng
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
Xinrun Wang
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
Xiaolei Zhang
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
Zhihong Zuo
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
Li Li
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha, Changsha 410008, China; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha 410008, China
Zhanwen Wang
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha, Changsha 410008, China; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha 410008, China
Wenxuan Zou
College of Life Sciences, Wuhan University, Wuhan 430072, China
Zhonghua Hu
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha, Changsha 410008, China; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha 410008, China; Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; Corresponding author
Zhaoxin Qian
Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital) Changsha, Changsha 410008, China; Hunan Provincial Clinical Research Center for Critical Care Medicine, Changsha 410008, China; Corresponding author
Summary: Dysregulated cardiac function after sepsis in intensive care unit is known to predict poor long-term outcome and increase mortality. Their pathological feature and molecular mechanism remain unclear. We observed that septic patients with depressed left ventricular ejection fraction (LVEF) have the highest in-hospital and 28 days mortality comparing to patients with hyperdynamic LVEF or with heart failure with preserved LVEF. Echocardiograms reveal that survivors post cecum ligation and puncture (CLP) on rodents have stable LVEF and non-survivors have fluctuated LVEF at CLP early phase. CLP-induced mice fall into three groups based on LVEF 24 h post-surgery: high-, low-, and normal-LVEF. Transcriptomic and proteomic analyses identify jointly and distinctively changed genes, proteins and biologically essential pathways in left ventricles from three CLP groups. Notably, transmission electron microscopy shows different mitochondrial and sarcomere defects associated with LVEF variances. Together, this study systematically characterizes the molecular, morphological, and functional alterations in CLP-induced cardiac injury.
