Mediating effects of platelet-derived extracellular vesicles on PM_(2.5)-induced vascular endothelial injury

摘要

At present, PM2.5 exposure has been considered as a major risk factor for cardiovascular disease. Most studies have focused on the toxic mechanism of PM2.5 in direct contact with cells or biomolecules, only few studies have reported the toxic mechanism of PM2.5 mediated by intercellular communication. Extracellular vesicles are the main carriers of intercellular communication and signal transduction in vivo, and play a vital role in the occurrence and development of cardiovascular disease. Therefore, the present research aimed to determine whether platelets-derived extracellular vesicles (P-EVs) secreted from PM2.5-exposed platelets are transferred into the human umbilical vein endothelial cells (HUVECs) and mediated the PM2.5-induced vascular endothelial injury by affecting normal cellular function. The result showed that P-EVs secreted from PM2.5-exposed platelets significantly reduced the proliferation promoting effect of normal P-EVs on vascular endothelium by decreasing the effective factors promoting vascular endothelial growth. Meanwhile, the levels of intercellular adhesion molecules, proinflammatory factors (ICAM-1, IL-6, and TNF-alpha) and the ROS level of HUVECs were markedly elevated. In addition, the apoptotic rate was increased via up-regulating the protein level of cytochrome-C(Cyt C), Bax, cleaved caspase-3 and down-regulating Bcl-2 in HUVECs, indicating that mitochondrial apoptotic pathway was activated by P-EVs secreted from PM2.5-exposed platelets. Further, the expression level of P-EVs targeted miRNAs in HUVECs was altered, indicating that miRNAs released from P-EVs were transferred to HUVECs and regulated the cellular function, while PM2.5 could inhibit this regulatory effect. In summary, these results demonstrate that the P-EVs secreted from PM2.5-exposed platelets can enter the HUVECs, which mediate the PM2.5-induced vascular endothelial injury. These findings provide a new perspective and theoretical basis for further exploring the mechanism of cardiovascular damage caused by PM2.5 exposure.