人体血管有机体揭示了CTGF在维护微血管完整性方面发挥的关键作用

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Sara G Romeo¹, Ilaria Secco¹, Edoardo Schneider¹

¹King's College London British Heart Foundation Centre, School of Cardiovascular & Metabolic Medicine and Sciences, London, UK.

Nature communications

|September 9, 2023

概括

人类血管有机体 (BVO) 模拟了微血管结构. 向糖解激活剂PFKFB3导致了快速的BVO重组,揭示了CTGF是微血管完整性的关键.

科学领域:

生物医学工程生物医学工程
血管生物学血管生物学
代谢研究研究代谢研究

背景情况:

微血管系对于组织输液和营养物质/气体交换至关重要.
人类血管有机体 (BVO) 为研究微血管功能提供了一个模型.
内皮细胞代谢,特别是糖解,对于微血管健康至关重要.

研究的目的:

通过使用BVO来研究糖解在微血管完整性中的作用.
探索向糖解激活剂PFKFB3对BVO结构和功能的影响.
为了确定微血管改造的关键调节者,以应对代谢变化.

主要方法:

代谢流量测试和13C-葡萄糖追踪以分析细胞代谢.
药物抑制和基因突变的PFKFB3在BVO.
对BVO分泌物的蛋白质组分析和细胞外矩阵重塑的评估.
用重组CTGF进行治疗,以评估其对微血管结构的影响.

主要成果:

BVO 显示依赖于糖溶性新陈代谢,反映了人类的微血管结构.
抑制或突变PFKFB3诱导了快速的BVO重组和船只回归.
秘密组分析显示了细胞外基质重塑和改变的膜介质表达,包括CTGF.
重组CTGF治疗挽救了微血管结构.

结论:

在研究微血管对代谢转变的反应方面,BVO是一个有价值的模型.
通过PFKFB3介导的糖解对于维持微血管完整性至关重要.
CTGF被认为是微血管结构和修复必不可少的关键膜调节器.

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