An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction.
An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction.
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DOI：
10.1084/jem.20051207
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发表时间：
2006-01-23
期刊：
影响因子：
--
通讯作者：
Ward PA
中科院分区：
文献类型：
--
作者：
Niederbichler AD;Hoesel LM;Westfall MV;Gao H;Ipaktchi KR;Sun L;Zetoune FS;Su GL;Arbabi S;Sarma JV;Wang SC;Hemmila MR;Ward PA
脓毒症期间的心脏功能缺陷被称为“脓毒症心肌病”。众所周知，脓毒症会导致补体系统的强烈激活。在当前的研究中，对盲肠结扎穿刺（CLP）后的大鼠的心脏功能和心肌细胞收缩力进行了评估。体内左心室压力和体外心肌细胞收缩力显着降低。在给予 C5a 阻断抗体的 CLP 大鼠中，这些缺陷得到了预防。 C5a 受体 (C5aR) 的 mRNA 和蛋白质均在心肌细胞上组成型表达； CLP 后两者均随时间而增加。体外添加重组大鼠 C5a 可在假心肌细胞和 CLP 心肌细胞中诱导显着的收缩功能障碍，但在来自 CLP 动物的细胞中诱导程度始终较高。这些数据表明，CLP 诱导心肌细胞上的 C5aR，并且 C5a 的体内生成导致 C5a-C5aR 相互作用，导致心肌细胞功能障碍，导致心脏功能受损。
Defective cardiac function during sepsis has been referred to as “cardiomyopathy of sepsis.” It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiomyocyte contractility in vitro. These defects were prevented in CLP rats given blocking antibody to C5a. Both mRNA and protein for the C5a receptor (C5aR) were constitutively expressed on cardiomyocytes; both increased as a function of time after CLP. In vitro addition of recombinant rat C5a induced dramatic contractile dysfunction in both sham and CLP cardiomyocytes, but to a consistently greater degree in cells from CLP animals. These data suggest that CLP induces C5aR on cardiomyocytes and that in vivo generation of C5a causes C5a–C5aR interaction, causing dysfunction of cardiomyocytes, resulting in compromise of cardiac performance.
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影响因子：
15.9
作者：
Guo, RF;Huber-Lang, M;Ward, PA
通讯作者：
Ward, PA
影响因子：
6
作者：
Laudes, IJ;Chu, JC;Ward, PA
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影响因子：
15.3
作者：
QUEZADO, ZMN;HOFFMAN, WD;NATANSON, C
通讯作者：
NATANSON, C
DOI：
10.1152/ajpregu.1998.275.2.r502
发表时间：
1998-08-01
影响因子：
2.8
作者：
Meng, XZ;Ao, LH;Harken, AH
通讯作者：
Harken, AH
DOI：
10.1016/s0022-2828(03)00004-x
发表时间：
2003-03-01
影响因子：
5
作者：
Mink, SN;Jacobs, H;Light, RB
通讯作者：
Light, RB