CXCL12信号传导对于心室冠状动脉内皮丛的成熟和功能性冠状动脉循环的建立至关重要。
CXCL12 Signaling Is Essential for Maturation of the Ventricular Coronary Endothelial Plexus and Establishment of Functional Coronary Circulation.
作者信息
Cavallero Susana, Shen Hua, Yi Christopher, Lien Ching-Ling, Kumar S Ram, Sucov Henry M
机构信息
Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.
出版信息
Dev Cell. 2015 May 26;33(4):469-77. doi: 10.1016/j.devcel.2015.03.018.
Maturation of a vascular plexus is a critical and yet incompletely understood process in organ development, and known maturation factors act universally in all vascular beds. In this study, we show that CXCL12 is an organ-specific maturation factor of particular relevance in coronary arterial vasculature. In vitro, CXCL12 does not influence nascent vessel formation, but promotes higher-order complexity of preinitiated vessels. In the heart, CXCL12 is expressed principally by the epicardium, and its receptor CXCR4 is expressed by coronary endothelial cells. CXCL12 is not a chemotactic signal for endothelial cell migration, but rather acts in a paracrine manner to influence the maturation of the coronary vascular plexus. Mutants in CXCL12 signaling show an excess of immature capillary chains and a selective failure in arterial maturation, and become leaky with the onset of coronary perfusion. Failed maturation of the coronary system explains the late-gestation lethality of these mutants.
血管丛的成熟是器官发育过程中一个关键但尚未完全理解的过程，已知的成熟因子在所有血管床中普遍起作用。在本研究中，我们表明CXCL12是冠状动脉血管系统中特别相关的器官特异性成熟因子。在体外，CXCL12不影响新生血管形成，但促进预先启动的血管的高阶复杂性。在心脏中，CXCL12主要由心外膜表达，其受体CXCR4由冠状动脉内皮细胞表达。CXCL12不是内皮细胞迁移的趋化信号，而是以旁分泌方式作用以影响冠状动脉丛的成熟。CXCL12信号通路中的突变体显示出过多的未成熟毛细血管链和动脉成熟的选择性失败，并在冠状动脉灌注开始时变得渗漏。冠状动脉系统成熟失败解释了这些突变体在妊娠后期的致死性。
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