Abstract：
UNASSIGNED: PM2.5 is closely linked to vascular endothelial injury and has emerged as a major threat to human health. Our previous research indicated that exposure to PM2.5 induced an increased release of miR-421 from the bronchial epithelium. However, the role of miR-421 in PM2.5-induced endothelial injury remains elusive.
UNASSIGNED: We utilized a subacute PM2.5-exposure model in mice in vivo and an acute injury cell model in vitro to simulate PM2.5-associated endothelial injury. We also used quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry to investigate the role of miR-421 in PM2.5-induced endothelial injury.
UNASSIGNED: Our findings reveal that inhibition of miR-421 attenuated PM2.5-induced endothelial injury and hypertension. Mechanistically, miR-421 inhibited the expression of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein endothelial cells and upregulated the expression of the downstream molecule inducible nitric oxide synthase (iNOS), thereby exacerbating PM2.5-induced endothelial injury.
UNASSIGNED: Our results indicate that PM2.5 exposure facilitates crosstalk between bronchial epithelial and endothelial cells via miR-421/ACE2/iNOS signaling pathway, mediating endothelial damage and hypertension. MiR-421 inhibition may offer a new strategy for the prevention and treatment of PM2.5-induced vascular endothelial injury.
UNASSIGNED: We utilized a subacute PM2.5-exposure model in mice in vivo and an acute injury cell model in vitro to simulate PM2.5-associated endothelial injury. We also used quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry to investigate the role of miR-421 in PM2.5-induced endothelial injury.
UNASSIGNED: Our findings reveal that inhibition of miR-421 attenuated PM2.5-induced endothelial injury and hypertension. Mechanistically, miR-421 inhibited the expression of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein endothelial cells and upregulated the expression of the downstream molecule inducible nitric oxide synthase (iNOS), thereby exacerbating PM2.5-induced endothelial injury.
UNASSIGNED: Our results indicate that PM2.5 exposure facilitates crosstalk between bronchial epithelial and endothelial cells via miR-421/ACE2/iNOS signaling pathway, mediating endothelial damage and hypertension. MiR-421 inhibition may offer a new strategy for the prevention and treatment of PM2.5-induced vascular endothelial injury.
摘要：
■PM2.5与血管内皮损伤密切相关，已成为人类健康的主要威胁。我们先前的研究表明，暴露于PM2.5会导致支气管上皮中miR-421的释放增加。然而,miR-421在PM2.5诱导的内皮损伤中的作用尚不清楚.
■我们利用小鼠体内亚急性PM2.5暴露模型和体外急性损伤细胞模型来模拟PM2.5相关的内皮损伤。我们还使用了定量实时聚合酶链反应，westernblot,酶联免疫吸附测定，和免疫组化研究miR-421在PM2.5诱导的内皮损伤中的作用。
■我们的研究结果表明，抑制miR-421可以减轻PM2.5诱导的内皮损伤和高血压。机械上,miR-421抑制人脐静脉内皮细胞血管紧张素转换酶2(ACE2)的表达,上调下游分子诱导型一氧化氮合酶(iNOS)的表达,从而加剧PM2.5诱导的内皮损伤。
■我们的结果表明，PM2.5暴露通过miR-421/ACE2/iNOS信号通路促进支气管上皮细胞和内皮细胞之间的串扰，介导内皮损伤和高血压。抑制MiR-421可能为PM2.5诱导的血管内皮损伤的防治提供新的策略。
■我们利用小鼠体内亚急性PM2.5暴露模型和体外急性损伤细胞模型来模拟PM2.5相关的内皮损伤。我们还使用了定量实时聚合酶链反应，westernblot,酶联免疫吸附测定，和免疫组化研究miR-421在PM2.5诱导的内皮损伤中的作用。
■我们的研究结果表明，抑制miR-421可以减轻PM2.5诱导的内皮损伤和高血压。机械上,miR-421抑制人脐静脉内皮细胞血管紧张素转换酶2(ACE2)的表达,上调下游分子诱导型一氧化氮合酶(iNOS)的表达,从而加剧PM2.5诱导的内皮损伤。
■我们的结果表明，PM2.5暴露通过miR-421/ACE2/iNOS信号通路促进支气管上皮细胞和内皮细胞之间的串扰，介导内皮损伤和高血压。抑制MiR-421可能为PM2.5诱导的血管内皮损伤的防治提供新的策略。
