MiR-939-5p suppresses PM_2.5-induced endothelial injury via targeting HIF-1α in HAECs

Abstract

Ambient air pollution is a leading cause of non-communicable disease in the world. PM_2.5 has the potential to change the miRNAs profiles, which in turn causes cardiovascular effects. Hypoxia-inducible factor (HIF)-1 plays a critical role in the development of atherosclerosis. Yet, the possible role of miR-939-5p/HIF-1α in PM_2.5-induced endothelial injury remains elusive. Therefore, the study aims to investigate the effects of miR-939-5p and HIF-1α on PM_2.5-triggered endothelial injury. The results from immunofluorescence, qRT-PCR, LSCM, and western blot assays demonstrated that PM_2.5 increased the levels of HIF-1α, inflammation and apoptosis in human aortic endothelial cells (HAECs). Yet, the inflammatory response and mitochondrial-mediated apoptosis pathway were effectively inhibited in HIF-1α knockdown HAECs lines. The expression of miR-939-5p was significantly down-regulated in HAECs after exposed to PM_2.5. The luciferase reporter, qRT-PCR and western blot results demonstrated that miR-939-5p could directly targeted HIF-1α. And the miR-939-5p overexpression restricted PM_2.5-triggered decreases in cell viability and increases in lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and inflammation. In addition, miR-939-5p overexpression remarkably suppressed PM_2.5-triggered BcL-2/Bax ratio reduction and Cytochrome C, Cleaved Caspase-9 and Cleaved Caspase-3 expression increase, revealed that miR-939-5p hampered PM_2.5-induced endothelial apoptosis through mitochondrial-mediated apoptosis pathway. Our results demonstrated that PM_2.5 increased the expression of HIF-1α followed by a pro-inflammatory and apoptotic response in HAECs. The protective effect of miR-939-5p on PM_2.5-triggered endothelial cell injury by negatively regulating HIF-1α. miR-939-5p might present a new therapeutic target for PM_2.5 induced endothelial injury.

Keywords:

• PM_2.5
• HAECs
• miR-939-5p
• hypoxia-inducible factor
• endothelial injury

Disclosure statement

The authors declare they have no conflict of interest.

Additional information

Funding

This work was supported by National Key Research and Development Program of China [2017YFC0211600, 2017YFC0211602, and 2017YFC0211606], National Natural Science Foundation of China [91943301 and 92043301], Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education [KZ202110025040], and Beijing Outstanding Talent Training Program.