Institute of Mechanobiology & Medical Engineering, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FASEB J. 2020 Oct;34(10):13586-13596. doi: 10.1096/fj.202000581R. Epub 2020 Aug 28.
Endothelial microparticles (EMPs) are involved in various cardiovascular pathologies and play remarkable roles in communication between endothelial cells (ECs), which are constantly exposed to mechanical cyclic stretch (CS) following blood pressure. However, the roles of EMPs induced by CS in EC homeostasis are still unclear. Both fluorescence resonance energy transfer (FRET) and western blotting revealed the activation of Src in ECs was significantly increased by 5% CS-induced EMPs. Furthermore, proteomic analysis revealed that the contents were obvious different in the EMPs between 5%- and 15%-group. Based on the bioinformatic analysis, CD151 on EMPs was predicted to activate Src, which was further confirmed by both FRET and western blotting. Moreover, the expression of CD151 on EMPs was significantly increased by 5% CS and involved in the binding of EMPs to ECs. EC apoptosis, which was significantly decreased by 5% CS-derived EMPs, showed obvious increase after pretreatment with Src inhibitor in target ECs. Our present research suggests that mechanical stretch changes the components of EMPs, which in turn modulates EC apoptosis by Src activation. CD151 expressed on CS-induced EMPs may play important roles in EC communication and homeostasis.
内皮细胞来源的微颗粒(EMPs)参与多种心血管病理过程,在血管内皮细胞(ECs)之间的通讯中发挥重要作用,而 ECs 一直处于血压引起的机械循环拉伸(CS)下。然而,CS 诱导的 EMPs 在 EC 稳态中的作用仍不清楚。荧光共振能量转移(FRET)和 Western blot 均显示,5% CS 诱导的 EMPs 显著增加了 EC 中 Src 的激活。此外,蛋白质组学分析显示,在 5%-和 15%-组之间 EMPs 的含量明显不同。基于生物信息学分析,预测 EMPs 上的 CD151 可激活 Src,这一预测通过 FRET 和 Western blot 得到了进一步证实。此外,5% CS 可显著增加 EMPs 上 CD151 的表达,并参与 EMPs 与 ECs 的结合。5% CS 衍生的 EMPs 可显著减少 EC 凋亡,而在靶 ECs 中用 Src 抑制剂预处理后,凋亡明显增加。本研究表明,机械拉伸改变了 EMPs 的成分,进而通过 Src 激活调节 EC 凋亡。CS 诱导的 EMPs 上表达的 CD151 可能在 EC 通讯和稳态中发挥重要作用。