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Mesenchymal-endothelial transition contributes to cardiac neovascularization

机译：间充质-内皮过渡有助于心脏新血管形成

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摘要

Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial- to - mesenchymal transition, but injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial-cell-like phenotype after acute ischaemic cardiac injury. Fibroblast-derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal- to-endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.%心肌成纤维细胞被认为是终末分化的细胞。现在，Arjun Deb及同事发现，心肌受伤会促使这些成纤维细胞发生“间质—内皮转化”(MEndoT)，获得与内皮细胞相似的命运，这个过程部分是由一个依赖于p53的机制介导的。他们发现，通过p53删除来降低MEndoT，在缺血性损伤之后会导致血管密度降低，也会导致心脏功能恶化。相反，p53的一个小分子激活因子的使用会增加MEndoT，导致对心脏功能的更好保持和减少结痂。
机译：内皮细胞通过经历了从内皮到间充质的转变，从而为心脏成纤维细胞的一个子集做出了贡献，但损伤尚不清楚。在这里，使用遗传命运图技术，我们证明了心脏成纤维细胞在急性缺血性心脏损伤后迅速采用了内皮细胞样表型。成纤维细胞来源的内皮细胞表现出天然内皮细胞的解剖学和功能特征。我们表明，转录因子p53调节心脏成纤维细胞命运的这种转换。心脏成纤维细胞中p53的丧失严重降低了成纤维细胞衍生的内皮细胞的形成，降低了梗死后的血管密度，并使心脏功能恶化。相反，刺激心脏成纤维细胞中的p53途径可增强间充质向内皮的转化，增强血管性并改善心脏功能。这些观察结果表明，间充质向内皮的转变有助于受伤心脏的新生血管形成，并代表了增强心脏修复的潜在治疗靶标。现在，Arjun Deb和同事发现，心肌损伤会引起这些成纤维细胞发生“间质—二醇转化”（MEndoT），获得与膀胱细胞相似的命运，这个过程部分是由一个依赖于p53的机制介导的。降低，MendoT，在收缩性损伤之后会导致血管密度降低，相反，也会导致心脏功能恶化。

著录项

  • 来源
    《Nature》 |2014年第7524期|585-590b1|共7页
  • 作者

    Eric Ubil; Jinzhu Duan; Indulekha C. L. Pillai; Manuel Rosa-Garrido; Yong Wu; Francesca Bargiacchi; Yan Lu; Seta Stanbouly; Jie Huang; Mauricio Rojas; Thomas M. Vondriska; Enrico Stefani; Arjun Deb;

  • 作者单位

    Department of Cell Biology & Physiology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Eli and Edythe Broad Institute of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA,Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, California 90095, USA,Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, USA,Molecular Biology Institute, University of California, Los Angeles, California 90095, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Eli and Edythe Broad Institute of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA,Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, California 90095, USA,Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, USA,Molecular Biology Institute, University of California, Los Angeles, California 90095, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;

    Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;

    Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Eli and Edythe Broad Institute of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA,Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, California 90095, USA,Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, USA,Molecular Biology Institute, University of California, Los Angeles, California 90095, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Eli and Edythe Broad Institute of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA,Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, California 90095, USA,Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, USA,Molecular Biology Institute, University of California, Los Angeles, California 90095, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Eli and Edythe Broad Institute of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA,Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, California 90095, USA,Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, USA,Molecular Biology Institute, University of California, Los Angeles, California 90095, USA;

    Department of Medicine, McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina 27599, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Molecular Biology Institute, University of California, Los Angeles, California 90095, USA,Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;

    Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Division of Molecular Medicine, Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;

    Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Cardiovascular Research Laboratory, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA,Eli and Edythe Broad Institute of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California 90095, USA,Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, California 90095, USA,Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, USA,Molecular Biology Institute, University of California, Los Angeles, California 90095, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 入库时间 2022-08-18 02:53:13

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