Cardiomyocyte-derived CXCL12 is not involved in cardiogenesis but plays a crucial role in myocardial infarction
Cardiomyocyte-derived CXCL12 is not involved in cardiogenesis but plays a crucial role in myocardial infarction
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DOI：
10.1007/s00109-016-1432-1
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发表时间：
2016-09-01
影响因子：
4.7
通讯作者：
Bader, Michael
中科院分区：
文献类型：
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作者：
Muehlstedt, Silke;Ghadge, Santhosh K.;Bader, Michael
趋化因子CXCL 12/SDF-1对心脏发育至关重要，并且由于其吸引白细胞和干细胞到受损心肌的能力而影响心脏修复过程。然而，CXCL 12在心肌梗死（MI）后是否有益还是有害存在很大争议。报道的CXCL 12作用的差异可能是由于MI后趋化因子的细胞来源和释放时间。本研究旨在评估心肌细胞衍生的CXCL 12在心肌梗死后心脏发生和心脏修复中的作用。我们生成了两种啮齿动物模型，每种模型仅在一种心脏细胞类型中靶向CXCL 12：心肌细胞特异性CXCL 12过表达转基因（Tg）大鼠和CXCL 12条件性敲除（cKO）小鼠。两种模型的动物在基线条件下均未显示任何心脏异常体征。在诱导MI后，cKO小鼠显示保留的心脏功能和重构。此外，心肌梗死后cKO小鼠心脏中的纤维化不太明显。因此，CXCL 12 Tg大鼠显示MI后心脏功能受损，伴有纤维化增强。此外，我们观察到cKO小鼠心脏中浸润的T（h）1细胞数量减少。总的来说，我们的研究结果表明，心肌细胞衍生的CXCL 12不参与心脏发育，但通过促进炎症和纤维化对损伤后的心脏产生不利影响。
The chemokine CXCL12/SDF-1 is crucial for heart development and affects cardiac repair processes due to its ability to attract leukocytes and stem cells to injured myocardium. However, there is a great controversy whether CXCL12 is beneficial or detrimental after myocardial infarction (MI). The divergence in the reported CXCL12 actions may be due to the cellular source and time of release of the chemokine after MI. This study was designed to evaluate the role of cardiomyocyte-derived CXCL12 for cardiogenesis and heart repair after MI. We generated two rodent models each targeting CXCL12 in only one cardiac cell type: cardiomyocyte-specific CXCL12-overexpressing transgenic (Tg) rats and CXCL12 conditional knockout (cKO) mice. Animals of both models did not show any signs of cardiac abnormalities under baseline conditions. After induction of MI, cKO mice displayed preserved cardiac function and remodeling. Moreover, fibrosis was less pronounced in the hearts of cKO mice after MI. Accordingly, CXCL12 Tg rats revealed impaired cardiac function post-MI accompanied by enhanced fibrosis. Furthermore, we observed decreased numbers of infiltrating T(h)1 cells in the hearts of cKO mice. Collectively, our findings demonstrate that cardiomyocyte-derived CXCL12 is not involved in cardiac development but has adverse effects on the heart after injury via promotion of inflammation and fibrosis.