Effects of extracellular histones on left ventricular diastolic function and potential mechanisms in mice with sepsis.
Effects of extracellular histones on left ventricular diastolic function and potential mechanisms in mice with sepsis.
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细胞外组蛋白对脓毒症小鼠左心室舒张功能的影响及潜在机制。
DOI：
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发表时间：
2022
影响因子：
2.2
通讯作者：
Guangping Li
中科院分区：
文献类型：
--
作者：
Lijun Wang;Ziyi Wang;Xing Liu;Yue Zhang;Manman Wang;Xue Liang;Guangping Li
细胞外组蛋白（EH）参与脓毒性心肌损伤（SMI）的发展。在本研究中，我们通过动物模型的体内和体外实验，探讨EH是否可诱导脓毒症患者左心室舒张功能障碍（LVDD），并探讨其潜在机制。采用超声心动图测量盲肠结扎穿孔（CLP）和eh治疗的雄性C57BL/6J小鼠左室舒张末期容积和等容松弛时间（IVRT）。采用酶联免疫吸附法、qRT-PCR和western blotting检测左心室组织/心肌细胞中凋亡相关蛋白（cleaved caspase-3、Bcl-2和Bax）和心肌肌钙蛋白T （cTnT）的蛋白和mRNA水平。流式细胞术检测心肌细胞凋亡。CLP小鼠出现LVDD，并伴有循环组蛋白、cTnT和Bax蛋白水平升高。CLP小鼠循环组蛋白与cTnT、Bax、IVRT和E/A比值相关。腹腔注射EH可导致小鼠LVDD。EH诱导心肌细胞凋亡，组蛋白中和剂改善SMI并保护小鼠免受CLP和EH诱导的死亡。EH参与脓毒性LVDD，这种改变可能与EH诱导的细胞凋亡有关。EH可能是重度精神分裂症的潜在治疗靶点。
Extracellular histone (EH) is involved in the development of septic myocardial injury (SMI). In this study, we explored whether EH could induce left ventricular diastolic dysfunction (LVDD) in sepsis, and investigated the potential mechanisms through in vivo and in vitro experiments using animal models.The ratio between E-wave and A-wave (E/A ratio), left ventricular end diastolic volume, and isovolumic relaxation time (IVRT) were measured in cecal ligation and perforation (CLP)- and EH-treated male C57BL/6J mice using echocardiography. The protein and mRNA levels of apoptosis-related proteins (cleaved caspase-3, Bcl-2, and Bax) and cardiac troponin T (cTnT) in the left ventricular tissue/cardiomyocytes were measured using enzyme-linked immunosorbent assay, qRT-PCR, and western blotting. Cardiomyocyte apoptosis was detected by flow cytometry.CLP mice presented with LVDD, which was accompanied by increased circulating histones, cTnT and Bax protein levels. Circulating histones were correlated with cTnT, Bax, IVRT, and E/A ratio in CLP mice. Intraperitoneal injection of EH resulted in LVDD in mice. EH induced cardiomyocyte apoptosis, and histone neutralizing agents improved SMI and protected mice against CLP- and EH-induced death.EH is involved in septic LVDD, and this alteration might be associated with EH-induced apoptosis. EH may serve as a potential therapeutic target for SMI.
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影响因子：
4.4
作者：
Fattahi, Fatemeh;Grailer, Jamison J.;Jajou, Lawrence;Zetoune, Firas S.;Andjelkovic, Anuska V.;Ward, Peter A.
通讯作者：
Ward, Peter A.
严重败血症患者和败血性休克患者的心室舒张功能障碍的预后价值。
影响因子：
--
作者：
Rolando G;Espinoza ED;Avid E;Welsh S;Pozo JD;Vazquez AR;Arzani Y;Masevicius FD;Dubin A
通讯作者：
Dubin A
影响因子：
3.6
作者：
M. Rodríguez-González;A. A. Perez-Reviriego-A.;Ana Castellano-Martínez;S. Lubián-López;Isabel Benavente-Fernández
通讯作者：
M. Rodríguez-González;A. A. Perez-Reviriego-A.;Ana Castellano-Martínez;S. Lubián-López;Isabel Benavente-Fernández
影响因子：
4.3
作者：
Lan Zhang;D. Xing;Lei Liu;Xuejuan Gao;Miaojuan Chen
通讯作者：
Lan Zhang;D. Xing;Lei Liu;Xuejuan Gao;Miaojuan Chen
影响因子：
37.8
作者：
Lancel, S;Joulin, O;Neviere, R
通讯作者：
Neviere, R