Angiogenic Function of Human Placental Endothelial Cells in Severe Fetal Growth Restriction Is Not Rescued by Individual Extracellular Matrix Proteins.
Angiogenic Function of Human Placental Endothelial Cells in Severe Fetal Growth Restriction Is Not Rescued by Individual Extracellular Matrix Proteins.
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严重胎儿生长受限（FGR）的特征是异常血管生成导致胎盘血管阻力增加。内皮细胞（EC）和细胞外基质（ECM）之间的相互作用是血管生成复杂过程的关键。我们以前发现，胎盘间质异常有助于严重FGR的血管生成受损。本研究的目的是更好地表征个别ECM蛋白对重度FGR背景下胎盘血管生成特性的影响。从人胎盘中分离出内皮细胞，无论是对照还是受严重FGR影响，并进行一系列实验以询问ECM蛋白对粘附、增殖、迁移和凋亡的作用。我们发现受损的增殖和迁移的生长受限的EC。虽然个别基板并没有实质性的影响迁移能力，胶原蛋白I，III和IV部分减轻FGR EC中看到的增殖缺陷。对照组和FGR组内皮细胞之间的粘附和凋亡差异不明显。我们的研究结果表明，胎盘血管生成缺陷的特点是严重的FGR不能解释由一个单一的ECM蛋白，而是作为一个整体的胎盘基质。进一步研究基质成分、结构、硬度、生长因子隔离和重塑能力的影响对于更好地理解ECM在严重FGR中血管生成受损中的作用至关重要。
Severe fetal growth restriction (FGR) is characterized by increased placental vascular resistance resulting from aberrant angiogenesis. Interactions between endothelial cells (ECs) and the extracellular matrix (ECM) are critical to the complex process of angiogenesis. We have previously found that placental stromal abnormalities contribute to impaired angiogenesis in severe FGR. The objective of this research is to better characterize the effect of individual ECM proteins on placental angiogenic properties in the setting of severe FGR. ECs were isolated from human placentae, either control or affected by severe FGR, and subjected to a series of experiments to interrogate the role of ECM proteins on adhesion, proliferation, migration, and apoptosis. We found impaired proliferation and migration of growth-restricted ECs. Although individual substrates did not substantially impact migratory capacity, collagens I, III, and IV partially mitigated proliferative defects seen in FGR ECs. Differences in adhesion and apoptosis between control and FGR ECs were not evident. Our findings demonstrate that placental angiogenic defects that characterize severe FGR cannot be explained by a singular ECM protein, but rather, the placental stroma as a whole. Further investigation of the effects of stromal composition, architecture, stiffness, growth factor sequestration, and capacity for remodeling is essential to better understand the role of ECM in impaired angiogenesis in severe FGR.
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影响因子：
2.1
作者：
Chan PY;Morris JM;Leslie GI;Kelly PJ;Gallery ED
通讯作者：
Gallery ED
影响因子：
3.8
作者：
Chen, CP;Aplin, JD
通讯作者：
Aplin, JD
影响因子：
6.6
作者：
Lang, I;Pabst, MA;Desoye, G
通讯作者：
Desoye, G
DOI：
10.1136/archdischild-2022-325285
发表时间：
2023-04-26
影响因子：
4.4
作者：
Lingam, Ingran;Okell, Jade;David, Anna
通讯作者：
David, Anna
DOI：
10.1080/10623320490512093
发表时间：
2004-05-01
影响因子：
--
作者：
Dye, JF;Lawrence, L;Clark, P
通讯作者：
Clark, P