Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
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DOI：
10.1038/nm1613
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发表时间：
2007-08-01
期刊：
影响因子：
82.9
通讯作者：
Kalluri, Raghu
中科院分区：
文献类型：
--
作者：
Zeisberg, Elisabeth M.;Tarnavski, Oleg;Kalluri, Raghu
心脏纤维化与微血管系统的程度降低和正常心肌结构的破坏有关，是由细胞外基质的过度沉积引起的，这是由成纤维细胞的募集介导的。这些成纤维细胞的来源尚不清楚，目前尚无特异性抗纤维化疗法。在这里，我们表明，心脏纤维化与源自内皮细胞的成纤维细胞的出现有关，这表明内皮-间充质转化（EndMT）类似于胚胎心脏房室垫形成过程中发生的事件。转化生长因子-β 1（TGF-β 1）诱导内皮细胞进行EndMT，而骨形态发生蛋白7（BMP-7）保留内皮表型。在压力超负荷和慢性同种异体移植排斥反应的小鼠模型中，全身给予重组人BMP-7（rhBMP-7）可显着抑制EndMT和心脏纤维化的进展。我们的研究结果表明，EndMT有助于心脏纤维化的进展，rhBMP-7可用于抑制EndMT和干预与纤维化相关的慢性心脏病的进展。
Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-beta 1 (TGF-beta 1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in mouse models of pressure overload and chronic allograft rejection. Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis.