Infarct Fibroblasts Do Not Derive From Bone Marrow Lineages.
Infarct Fibroblasts Do Not Derive From Bone Marrow Lineages.
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DOI：
10.1161/circresaha.117.311490
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发表时间：
2018-02-16
影响因子：
20.1
通讯作者：
Evans SM
中科院分区：
文献类型：
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作者：
Moore-Morris T;Cattaneo P;Guimarães-Camboa N;Bogomolovas J;Cedenilla M;Banerjee I;Ricote M;Kisseleva T;Zhang L;Gu Y;Dalton ND;Peterson KL;Chen J;Pucéat M;Evans SM
心肌梗死（MI）是全球成人死亡的主要原因。构成梗死后瘢痕的心脏成纤维细胞的起源仍然存在争议，特别是骨髓谱系对瘢痕内活化成纤维细胞的潜在贡献。使用谱系追踪和骨髓移植以及心脏成纤维细胞的稳健标志物胶原1a 1-GFP报告基因来确定梗死成纤维细胞的起源。使用遗传谱系追踪或骨髓移植，我们没有发现证据表明，在永久性左前降支（LAD）冠状动脉结扎的心脏中，有来自造血或骨髓谱系的胶原产生成纤维细胞。事实上，梗死区域内的成纤维细胞主要是心外膜来源的。有趣的是，来自造血谱系的产生胶原的纤维细胞被观察到附着在梗塞和假手术心脏的心外膜表面，其中缝合线被放置在LAD周围。在这个有争议的领域，我们的研究表明，绝大多数梗死成纤维细胞是心外膜来源，而不是来自骨髓谱系，内皮细胞间质转化（EndoMT）或血液。我们还注意到心外膜表面存在产生胶原的纤维细胞，这至少部分是由外科手术引起的。
Myocardial infarction (MI) is a major cause of adult mortality worldwide. The origin(s) of cardiac fibroblasts that constitute the post-infarct scar remain controversial, in particular the potential contribution of bone marrow lineages to activated fibroblasts within the scar. To establish the origin(s) of infarct fibroblasts using lineage tracing and bone marrow transplants, and a robust marker for cardiac fibroblasts, the Collagen1a1-GFP reporter. Using genetic lineage tracing or bone marrow transplant, we found no evidence for Collagen-producing fibroblasts derived from hematopoietic or bone marrow lineages in hearts subjected to permanent left anterior descending (LAD) coronary artery ligation. In fact, fibroblasts within the infarcted area were largely of epicardial origin. Intriguingly, collagen-producing fibrocytes from hematopoietic lineages were observed attached to the epicardial surface of infarcted and sham-operated hearts in which a suture was placed around the LAD. In this controversial field, our study demonstrated that the vast majority of infarct fibroblasts were of epicardial origin and not derived from bone marrow lineages, endothelial-to-mesenchymal transition (EndoMT) or blood. We also noted the presence of collagen-producing fibrocytes on the epicardial surface that resulted at least in part from the surgical procedure.