Mediating effects of platelet-derived extracellular vesicles on PM_2.5-induced vascular endothelial injury

At present, PM_2.5 exposure has been considered as a major risk factor for cardiovascular disease. Most studies have focused on the toxic mechanism of PM_2.5 in direct contact with cells or biomolecules, only few studies have reported the toxic mechanism of PM_2.5 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 PM_2.5-exposed platelets are transferred into the human umbilical vein endothelial cells (HUVECs) and mediated the PM_2.5-induced vascular endothelial injury by affecting normal cellular function. The result showed that P-EVs secreted from PM_2.5-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-α) 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 PM_2.5-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 PM_2.5 could inhibit this regulatory effect. In summary, these results demonstrate that the P-EVs secreted from PM_2.5-exposed platelets can enter the HUVECs, which mediate the PM_2.5-induced vascular endothelial injury. These findings provide a new perspective and theoretical basis for further exploring the mechanism of cardiovascular damage caused by PM_2.5 exposure.