Bao H, Yao Q-P, Huang K, Chen X-H, Han Y, Jiang Z-L, Gao L-Z, Qi Y-X
Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Cell Mol Biol (Noisy-le-grand). 2017 Apr 29;63(4):3-9. doi: 10.14715/cmb/2017.63.4.1.
The dysfunction of endothelial cells (ECs) plays crucial roles in vascular remodeling during hypertension. Researches suggested that ECs are regulated by the circulating platelets in vivo, which may participate in abnormal EC apoptosis in hypertension. However the molecular mechanism in this process is still unclear. Here we focused on the microRNAs (miRs) in platelets, and detected the potential role and delivery mechanism of platelet-derived miRs in ECs. Using microarray, the differentially expressed profile of miRs between platelets and ECs was detected. The results revealed that compared with ECs, 67 miRs highly expressed in platelets including the most significant one- miR-142-3p. Since platelets are activated by thrombin in hypertension, we detected the miR-142-3p transferring mechanism of activated platelet, and proved that platelet-derived microparticles (PMPs), but not platelets directly, delivered miR-142-3p into ECs via cellular adherent. Furthermore, BCL2L1, an important molecule in cell apoptosis, was predicted to be a putative target of miR-142-3p by multiple algorithms. Dual luciferase reporter assays, as well as miR-142-3p mimics treatment were used to confirm the interplay between miR-142-3p and BCL2L1. Meanwhile, using in vivo hypertensive rat model, our results showed that the expression of platelet-derived miR-142-3p and the apoptosis were both significantly increased in ECs during hypertension. The present results suggested that platelet-derived miR-142-3p is delivered into ECs via PMPs, and may modulate the expression of target molecule- BCL2L1, which may subsequently display a negative function by modulating EC apoptosis in hypertension.
内皮细胞（ECs）功能障碍在高血压血管重塑过程中起关键作用。研究表明，ECs在体内受循环血小板调控，这可能参与了高血压中异常的EC凋亡。然而，这一过程中的分子机制仍不清楚。在此，我们聚焦于血小板中的微小RNA（miRs），并检测血小板源性miRs在ECs中的潜在作用及传递机制。通过微阵列检测血小板与ECs之间miRs的差异表达谱。结果显示，与ECs相比，血小板中有67种miRs高表达，其中最显著的是miR-142-3p。由于高血压中血小板被凝血酶激活，我们检测了活化血小板的miR-142-3p转移机制，证明是血小板源性微粒（PMPs）而非血小板直接通过细胞黏附将miR-142-3p递送至ECs。此外，通过多种算法预测细胞凋亡中的重要分子BCL2L1是miR-142-3p的假定靶标。采用双荧光素酶报告基因检测以及miR-142-3p模拟物处理来证实miR-142-3p与BCL2L1之间的相互作用。同时，利用体内高血压大鼠模型，我们的结果表明高血压期间ECs中血小板源性miR-142-3p的表达和凋亡均显著增加。目前的结果表明，血小板源性miR-142-3p通过PMPs递送至ECs，并可能调节靶分子BCL2L1的表达，随后可能通过调节高血压中的EC凋亡发挥负性作用。
