1. Propofol inhibits myocardial injury induced by microvesicles derived from hypoxiareoxygenated endothelial cells via lncCCT4-2/CCT4 signaling
- Author
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Zhang,Xiaojun, Wang,Changsen, Xu,Hao, Cai,Shuyun, Liu,Keyu, Li,Simeng, Chen,Linming, Shen,Siman, Gu,Xiaoxia, Tang,Jing, Xia,Zhengyuan, Hu,Zhe, Ma,Xiaotang, Zhang,Liangqing, Zhang,Xiaojun, Wang,Changsen, Xu,Hao, Cai,Shuyun, Liu,Keyu, Li,Simeng, Chen,Linming, Shen,Siman, Gu,Xiaoxia, Tang,Jing, Xia,Zhengyuan, Hu,Zhe, Ma,Xiaotang, and Zhang,Liangqing
- Abstract
Background Ischemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms. Methods Hypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay. Results In vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-inju
- Published
- 2023