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Lymphoangiocrine signals promote cardiac growth and repair

机译:淋巴血管病程促进心脏生长和修复

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摘要

Recent studies have suggested that lymphatics help to restore heart function after cardiac injury~(1-6). Here we report that lymphatics promote cardiac growth, repair and cardioprotection in mice. We show that a lymphoangiocrine signal produced by lymphatic endothelial cells (LECs) controls the proliferation and survival of cardiomyocytes during heart development, improves neonatal cardiac regeneration and is cardioprotective after myocardial infarction. Embryos that lack LECs develop smaller hearts as a consequence of reduced cardiomyocyte proliferation and increased cardiomyocyte apoptosis. Culturing primary mouse cardiomyocytes in LEC-conditioned medium increases cardiomyocyte proliferation and survival, which indicates that LECs produce lymphoangiocrine signals that control cardiomyocyte homeostasis. Characterization of the LEC secretome identified the extracellular protein reelin (RELN) as a key component of this process. Moreover, we report that LEC-specific Reln-null mouse embryos develop smaller hearts, that RELN is required for efficient heart repair and function after neonatal myocardial infarction, and that cardiac delivery of RELN using collagen patches improves heart function in adult mice after myocardial infarction by a cardioprotective effect. These results highlight a lymphoangiocrine role of LECs during cardiac development and injury response, and identify RELN as an important mediator of this function.
机译:最近的研究表明,淋巴管有助于心脏损伤后恢复心脏功能〜(1-6)。在这里,我们报告淋巴管促进小鼠的心脏生长,修复和心脏保护。我们表明,淋巴内皮细胞(LECs)产生的淋巴脊髓信号控制心脏发育过程中心肌细胞的增殖和存活,改善了新生儿心脏再生,并且心肌梗死后的心脏保护剂。由于减少的心肌细胞增殖和增加的心肌细胞凋亡,缺乏LECs的胚胎产生较小的心脏。在LEC条件培养基中培养初级小鼠心肌细胞增加了心肌细胞增殖和存活率,这表明LECS产生控制心肌细胞稳态的淋巴脊髓信号。 LEC沉淀的表征鉴定了细胞外蛋白reelin(Reln)作为该方法的关键组分。此外,我们报告了LEC特异性Reln-Null鼠标胚胎发育较小的心脏,即新生儿心肌梗死后有效的心脏修复和功能需要Reln,并且使用胶原蛋白斑块的Reln的心脏递送改善了心肌梗死后成年小鼠的心脏功能通过心脏保护作用。这些结果突出了LECs在心脏发育和伤害反应期间LEC的淋巴脊髓作用,并确定了该功能的重要介质。

著录项

  • 来源
    《Nature》 |2020年第7839期|705-711|共7页
  • 作者单位

    Center for Vascular and Developmental Biology Feinberg Cardiovascular and Renal Research Institute Feinberg School of Medicine Northwestern University;

    Cardiovascular Development Program Centro Nacional de Investigaciones Cardiovasculares CNIC;

    Department of Molecular Biology University of Texas Southwestern Medical Center;

    Department of Physiology Semmelweis University School of Medicine|MTA-SE "Lendulet" Lymphatic Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University Department of Physiology Semmelweis University School of Medicine;

    Center for Vascular and Developmental Biology Feinberg Cardiovascular and Renal Research Institute Feinberg School of Medicine Northwestern University;

    Department of Molecular Genetics University of Texas Southwestern Medical Center;

    Center for Vascular and Developmental Biology Feinberg Cardiovascular and Renal Research Institute Feinberg School of Medicine Northwestern University;

    Department of Pharmacology Feinberg School of Medicine Northwestern University;

    Department of Pathology Feinberg School of Medicine Northwestern University;

    Center for Vascular and Developmental Biology Feinberg Cardiovascular and Renal Research Institute Feinberg School of Medicine Northwestern University;

    Department of Pathology Feinberg School of Medicine Northwestern University;

    Department of Pharmacology Feinberg School of Medicine Northwestern University;

    Department of Physiology Semmelweis University School of Medicine|MTA-SE "Lendulet" Lymphatic Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University Department of Physiology Semmelweis University School of Medicine;

    Department of Molecular Genetics University of Texas Southwestern Medical Center|Department of Neuroscience University of Texas Southwestern Medical Center|Department of Neurology & Neurotherapeutics University of Texas Southwestern Medical Center;

    Department of Molecular Biology University of Texas Southwestern Medical Center;

    Cardiovascular Development Program Centro Nacional de Investigaciones Cardiovasculares CNIC;

    Center for Vascular and Developmental Biology Feinberg Cardiovascular and Renal Research Institute Feinberg School of Medicine Northwestern University;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
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