Alberta Children's Hospital Research Institute and Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Alberta Children's Hospital Research Institute and Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
Development. 2020 May 18;147(10):dev183061. doi: 10.1242/dev.183061.
The thin endothelial wall of a newly formed vessel is under enormous stress at the onset of blood flow, rapidly acquiring support from mural cells (pericytes and vascular smooth muscle cells; vSMCs) during development. Mural cells then develop vasoactivity (contraction and relaxation) but we have little information as to when this first develops or the extent to which pericytes and vSMCs contribute. For the first time, we determine the dynamic developmental acquisition of vasoactivity in the cerebral vasculature of zebrafish. We show that pericyte-covered vessels constrict in response to α-adrenergic receptor agonists and dilate in response to nitric oxide donors at 4 days postfertilization (dpf) but have heterogeneous responses later, at 6 dpf. In contrast, vSMC-covered vessels constrict at 6 dpf, and dilate at both stages. Using genetic ablation, we demonstrate that vascular constriction and dilation is an active response. Our data suggest that both pericyte- and vSMC-covered vessels regulate their diameter in early development, and that their relative contributions change over developmental time.
新形成的血管的薄内皮壁在血流开始时承受着巨大的压力，在发育过程中迅速获得壁细胞（周细胞和血管平滑肌细胞；vSMCs）的支持。然后，壁细胞会产生血管活性（收缩和舒张），但我们对其最初何时发展以及周细胞和 vSMCs 的贡献程度知之甚少。我们首次确定了斑马鱼脑血管中血管活性的动态发育获得。我们表明，在受精后 4 天（dpf），被周细胞覆盖的血管对 α-肾上腺素能受体激动剂收缩，并对一氧化氮供体舒张，但在 6 dpf 后反应不均匀。相比之下，被 vSMC 覆盖的血管在 6 dpf 时收缩，在两个阶段都舒张。通过基因消融，我们证明血管收缩和舒张是一种主动反应。我们的数据表明，周细胞和 vSMC 覆盖的血管都在早期发育中调节其直径，并且它们的相对贡献随着发育时间的变化而变化。
