Quercetin protects endothelial function from inflammation induced by localized disturbed flow by inhibiting NRP2 -VEGFC complex

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  • 作者:Wenying Zhou, Feng Wang, Xuesong Qian, Shuai Luo, Zhimei Wang, Xiaofei Gao, Xiangquan Kong, Junjie Zhang, Shaoliang Chen
  • 期刊:INTERNATIONAL IMMUNOPHARMACOLOGY
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Atherosclerosis is a focal chronic inflammatory disease, the initial pathogenic event of which is endothelial dysfunction, and disturbed flow (DF) is the primary and vital factor underlying endothelial dysfunction. The present research aims to elucidate the mechanism underlying the regulation of Neuropilin (NRP)2 under DF in endothelial cells (ECs) in an inflammatory state. We observed that NRP2 expression was significantly upregulated in DF-stimulated human umbilical vein endothelial cells (HUVECs). Knockdown of NRP2 in HUVECs significantly ameliorated cell inflammation induced by DF. In addition, quercetin inhibited NRP2 expression as well as endothelial inflammation. Animal experiments suggested that NRP2 knockdown or intraperitoneal injection of quercetin affected the expression of inflammation-related genes. Moreover, the upstream transcription factor GATA2 was found to regulate NRP2 transcription by binding to the ?1100 to +100?bp region of the NRP2 promoter. Further studies showed that quercetin inhibited NRP2-VEGFC complex formation induced by disturbed flow, although did not inhibit GATA2 expression. These findings suggest that NRP2 plays an important role in promoting inflammation. Quercetin antagonizes atherosclerosis by inhibiting NRP2 and the formation of NRP2-VEGFC complex by inhibiting the inflammatory effects induced by disordered flow.

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