Hypoxia regulate developmental coronary angiogenesis potentially through VEGF-R2- and SOX17-mediated signaling.

IF 2 3区 生物学 Q2 ANATOMY & MORPHOLOGY
Halie E Vitali, Bryce Kuschel, Chhiring Sherpa, Brendan W Jones, Nisha Jacob, Syeda A Madiha, Sam Elliott, Eddie Dziennik, Lily Kreun, Cora Conatser, Bhupal P Bhetwal, Bikram Sharma
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引用次数: 0

Abstract

Background: The development of coronary vessels in embryonic mouse heart involves various progenitor populations, including sinus venosus (SV), endocardium, and proepicardium. ELA/APJ signaling is known to regulate coronary growth from the SV, whereas VEGF-A/VEGF-R2 signaling controls growth from the endocardium. Previous studies suggest hypoxia might regulate coronary growth, but its specific downstream pathways are unclear. In this study, we further investigated the role of hypoxia and have identified SOX17- and VEGF-R2-mediated signaling as the potential downstream pathways in its regulation of developmental coronary angiogenesis.

Results: HIF-1α stabilization by knocking out von Hippel Lindau (VHL) protein in the myocardium (cKO) disrupted normal coronary angiogenesis in embryonic mouse hearts, resembling patterns of accelerated coronary growth. VEGF-R2 expression was increased in coronary endothelial cells under hypoxia in vitro and in VHL cKO hearts in vivo. Similarly, SOX17 expression was increased in the VHL cKO hearts, while its knockout in the endocardium disrupted normal coronary growth.

Conclusion: These findings provide further evidence that hypoxia regulates developmental coronary growth potentially through VEGF-R2 and SOX17 pathways, shedding light on mechanisms of coronary vessel development.

缺氧可能通过 VEGF-R2- 和 SOX17 介导的信号传导调节发育期冠状动脉血管生成。
背景:胚胎小鼠心脏冠状血管的发育涉及不同的祖细胞群,包括窦静脉(SV)、心内膜和原心包。已知 ELA/APJ 信号调节来自 SV 的冠状动脉生长,而 VEGF-A/VEGF-R2 信号则控制来自心内膜的冠状动脉生长。以前的研究表明,缺氧可能会调控冠状动脉的生长,但其具体的下游通路尚不清楚。在本研究中,我们进一步研究了缺氧的作用,并确定了SOX17和VEGF-R2介导的信号传导是其调控发育期冠状动脉血管生成的潜在下游途径:结果:通过敲除心肌中的von Hippel Lindau(VHL)蛋白(cKO)稳定HIF-1α,破坏了胚胎小鼠心脏正常的冠状动脉血管生成,类似于冠状动脉加速生长的模式。在体外缺氧和体内 VHL cKO 心脏中,冠状动脉内皮细胞中 VEGF-R2 的表达增加。同样,SOX17在VHL cKO心脏中的表达也增加了,而其在心内膜中的敲除破坏了冠状动脉的正常生长:这些发现进一步证明了缺氧可能通过VEGF-R2和SOX17途径调节冠状动脉的发育生长,从而揭示了冠状动脉血管发育的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Developmental Dynamics
Developmental Dynamics 生物-发育生物学
CiteScore
5.10
自引率
8.00%
发文量
116
审稿时长
3-8 weeks
期刊介绍: Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.
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