Parsons-Wingerter Patricia, McKay Terri L, Leontiev Dmitry, Vickerman Mary B, Condrich Terence K, Dicorleto Paul E
Research and Technology Directorate, National Aeronautics and Space Administration Glenn Research Center, Cleveland, Ohio 44135, USA.
Anat Rec A Discov Mol Cell Evol Biol. 2006 Mar;288(3):233-47. doi: 10.1002/ar.a.20309.
Development of effective vascular therapies requires the understanding of all modes of vessel formation involved in angiogenesis (here termed "hemangiogenesis") and lymphangiogenesis. Two major modes of vessel morphogenesis include sprouting of a new vessel from a preexisting vessel and splitting of a preexisting parent vessel into two offspring vessels. In the quail chorioallantoic membrane (CAM) during mid-development (embryonic days E6-E9), lymphangiogenesis progressed primarily via blind-ended vessel sprouting. Isolated lymphatic endothelial progenitor cells were recruited to the tips of growing vessels. During concurrent hemangiogenesis, parent blood vessels expanded from the capillary network and split into offspring vessels, accompanied by transient capillary expression of alpha smooth muscle actin (alphaSMA) and recruitment of polarized mural progenitor cells. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptor VEGFR-2, alphaSMA (specific to CAM blood vessels), homeobox transcription factor Prox1 (specific to lymphatics), and the quail hematopoetic marker, QH-1. VEGFR-2 was expressed intensely in isolated cells and lymphatics, and moderately in blood vessels. Prox1 was absent from isolated progenitor cells prior to lymphatic recruitment. Exogenous vascular endothelial growth factor-165 (VEGF165) increased blood vessel density and anastomotic frequency without changing endogenous modes of vascular/lymphatic vessel formation or marker expression. Although VEGF165 is a key cellular regulator of hemangiogenesis and vasculogenesis, the role of VEGF165 in lymphangiogenesis is less clear. Interestingly, VEGF165 increased lymphatic vessel diameter and density as measured by novel Euclidean distance mapping, and the antimaturational dissociation of lymphatics from blood vessels, accompanied by lymphatic reassociation into homogeneous networks.
有效的血管治疗方法的开发需要了解血管生成（此处称为“血管新生”）和淋巴管生成中涉及的所有血管形成模式。血管形态发生的两种主要模式包括从预先存在的血管中长出新血管以及将预先存在的母血管分裂为两个子血管。在发育中期（胚胎第6至9天）的鹌鹑绒毛尿囊膜（CAM）中，淋巴管生成主要通过盲端血管发芽进行。孤立的淋巴管内皮祖细胞被招募到生长血管的末端。在同时发生的血管新生过程中，母血管从毛细血管网络扩张并分裂为子血管，伴随着α平滑肌肌动蛋白（αSMA）的短暂毛细血管表达以及极化壁祖细胞的募集。通过对血管内皮生长因子（VEGF）受体VEGFR - 2、αSMA（特定于CAM血管）、同源盒转录因子Prox1（特定于淋巴管）和鹌鹑造血标志物QH - 1进行共聚焦/荧光显微镜检查来识别淋巴管和血管。VEGFR - 2在孤立细胞和淋巴管中强烈表达，在血管中中度表达。在淋巴管募集之前，孤立的祖细胞中不存在Prox1。外源性血管内皮生长因子 - 165（VEGF165）增加了血管密度和吻合频率，而没有改变血管/淋巴管形成的内源性模式或标志物表达。尽管VEGF165是血管新生和血管生成的关键细胞调节因子，但其在淋巴管生成中的作用尚不清楚。有趣的是，通过新颖的欧几里得距离映射测量，VEGF165增加了淋巴管直径和密度，以及淋巴管与血管的抗成熟解离，伴随着淋巴管重新组合成均匀的网络。
