Inhibition of Cyclooxygenase-2 Suppresses the Recruitment of Endothelial Progenitor Cells in the Microvasculature of Endometriotic Lesions.
Inhibition of Cyclooxygenase-2 Suppresses the Recruitment of Endothelial Progenitor Cells in the Microvasculature of Endometriotic Lesions.
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DOI：
10.1016/j.ajpath.2017.10.013
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Jeannette Rudzitis-Auth;R. Nickels;M. Menger;M. Laschke
中科院分区：
文献类型：
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作者：
Jeannette Rudzitis-Auth;R. Nickels;M. Menger;M. Laschke
内皮祖细胞（EPCs）进入新生血管有助于血管病变的血管化。我们分析了环氧合酶（考克斯）-2信号转导是否调控了这一血管发生过程。在辐照的FVB/N小鼠中手术诱导子宫内膜异位病变，所述小鼠用来自FVB/N-TgN [Tie 2/绿色荧光蛋白（GFP）] 287 Sato小鼠的骨髓重建。动物每周接受一次β-雌二醇17-戊酸酯，每天用选择性考克斯-2抑制剂帕瑞昔布（25 mg/kg）或溶剂（对照）治疗7天和28天。分析涉及通过高分辨率超声、卡尺测量、流式细胞术、组织学分析和免疫组织化学分析测定病变生长、囊肿形成、GFP+/Tie 2 +EPCs归巢、循环EPCs数量、血管形成、细胞增殖、凋亡和免疫细胞浸润。在帕瑞昔布治疗的小鼠中，血液循环中的EPCs较高，但与对照组相比，增生病变中招募的EPCs数量显著降低。这一发现与受损的早期血管形成和基质组织生长以及病变腺体分泌活动减少有关。帕瑞昔布治疗的病变进一步含有较少的增殖和更多的凋亡细胞，并表现出较低数量的浸润性巨噬细胞和嗜中性粒细胞。这些发现表明，抑制考克斯-2抑制血管生成的病变，这可能有助于受损的病变血管化和生长。
The incorporation of endothelial progenitor cells (EPCs) into newly developing blood vessels contributes to the vascularization of endometriotic lesions. We analyzed whether cyclooxygenase (COX)-2 signaling regulates this vasculogenic process. Endometriotic lesions were surgically induced in irradiated FVB/N mice, which were reconstituted with bone marrow from FVB/N-TgN [Tie2/green fluorescent protein (GFP)] 287 Sato mice. The animals received β-estradiol 17-valerate once a week and were treated daily with the selective COX-2 inhibitor parecoxib (25 mg/kg) or vehicle (control) for 7 and 28 days. Analyses involved the determination of lesion growth, cyst formation, homing of GFP+/Tie2+EPCs, numbers of circulating EPCs, vascularization, cell proliferation, apoptosis, and immune cell infiltration by means of high-resolution ultrasonography, caliper measurements, flow cytometry, histologic analysis, and immunohistochemical analysis. In parecoxib-treated mice, blood circulating EPCs were higher, but numbers of recruited EPCs in endometriotic lesions were significantly lower when compared with controls. This finding was associated with an impaired early vascularization and stromal tissue growth as well as reduced glandular secretory activity of the lesions. Parecoxib-treated lesions further contained less proliferating and more apoptotic cells and exhibited lower numbers of infiltrating macrophages and neutrophilic granulocytes. These findings demonstrate that the inhibition of COX-2 suppresses vasculogenesis in endometriotic lesions, which may contribute to an impaired lesion vascularization and growth.