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Endothelial heterogeneity of blood-brain barrier gene expression along the brain microvasculature.

机译：沿大脑微脉管系统的血脑屏障基因表达的内皮异质性。

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摘要

The blood-brain barrier (BBB) refers to the network of microvessels that selectively restricts the passage of substances between the circulation and central nervous system (CNS). This microvascular network is comprised of arterioles, capillaries and venules, yet the respective contribution of each of these to the BBB awaits clarification. In this regard, it has been postulated that brain microvascular endothelial cells (BMEC) from these different tributaries might exhibit considerable heterogeneity in form and function, with such diversity underlying unique roles in physiological and pathophysiological processes. Means to begin exploring such endothelial differences within the CNS in situ, free from caveats associated with cell isolation and culturing procedures, are crucial to comprehending the nature and treatment of CNS diseases with vascular involvement. Here, a unique approach was used to analyze BBB gene expression patterns of endothelial cells retrieved in situ from the distinct microvascular segments: immuno-laser capture microdissection (immuno-LCM) coupled to quantitative real-time PCR (qRT-PCR). After validating the reproducibility of this combined approach, an initial assessment of endothelial heterogeneity was obtained by contrasting expression patterns of a handful of BBB genes between arterioles, capillaries and venules. Due to the close proximity of smooth muscle cells to arteriolar BMEC and given the resolution of the PixCell Ile LCM machine, great difficulty was encountered in ensuring endothelial purity for this branch. For this reason, efforts focused on contrasting LCM-procured capillary versus venular BMEC for the full panorama of BBB genes. From profiling 87 genes encoding proteins shown to play a role in BE3B function or enriched in BMEC compared to parenchyma but with unknown contribution to BBB function, results imply that most BBB properties reside in both segments, but that capillaries preferentially express some genes related to solute transport, while venules tend toward higher expression of genes involved in inflammatory-related tasks. Moreover, preliminary studies support employing this approach to detect age-related differences in BBB gene expression. Performed under physiological conditions, these studies call attention to the breadth of endothelial diversity and its functional consequences with respect to the BBB and set the stage for the role played by endothelial heterogeneity under CNS disease.
机译：血脑屏障（BBB）是指微血管网络，可选择性地限制物质在循环系统和中枢神经系统（CNS）之间的通过。该微血管网络由小动脉，毛细血管和小静脉组成，但是尚需澄清它们各自对血脑屏障的贡献。在这方面，已经假定来自这些不同支流的脑微血管内皮细胞（BMEC）可能在形式和功能上表现出很大的异质性，这种多样性在生理和病理生理过程中具有独特的作用。没有任何与细胞分离和培养程序有关的警告的方法，就地开始探索CNS内这种内皮细胞差异的方法，对于理解血管介入的CNS疾病的性质和治疗至关重要。在这里，一种独特的方法被用来分析从不同的微血管部分原位回收的内皮细胞的BBB基因表达模式：免疫激光捕获显微切割术（immuno-LCM）结合定量实时PCR（qRT-PCR）。在验证了这种组合方法的可重复性之后，通过对比小动脉，毛细血管和小静脉之间的少数BBB基因的表达模式，获得了内皮异质性的初步评估。由于平滑肌细胞非常靠近小动脉BMEC，并且具有PixCell Ile LCM机器的分辨率，因此在确保该分支的内皮纯度方面遇到了很大困难。由于这个原因，我们的工作重点是对比LCM取得的毛细血管和静脉血BMEC，以了解BBB基因的全貌。通过分析87个编码蛋白质的基因，这些蛋白质显示出与实质相比在BE3B功能中起作用或在BMEC中富集，但对BBB功能的贡献未知，结果表明大多数BBB特性都存在于两个区段中，但毛细管优先表达一些与溶质相关的基因转运，而小静脉趋向于表达与炎症相关任务的基因。此外，初步研究支持采用这种方法来检测BBB基因表达中与年龄相关的差异。在生理条件下进行的这些研究引起了人们对内皮多样性的广度及其对BBB的功能性影响的关注，并为内皮异质性在中枢神经系统疾病中扮演的角色奠定了基础。

著录项

  • 作者

    Macdonald, Jennifer Alexandra.;

  • 作者单位

    University of Connecticut.;

  • 授予单位 University of Connecticut.;
  • 学科 Biology Molecular.;Biology Cell.;Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 245 p.
  • 总页数 245
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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