摘要

In this study, we aimed to scrutinize the link between the expression of circulating mir-367 and the NF-kappa B activated inflammatory pathway in the pathogenesis of coronary artery disease (CAD) and the potential underlying molecular mechanism. Plasma samples were collected from a single cohort of 60 CAD patients and 60 control subjects, and mir-367 levels in samples stemming from each study subject were examined by quantitative real-time PCR (qRT-PCR). Simultaneously, plasma TNF-alpha, IL-6 and NF-kappa B levels were measured by ELISA. Western blotting and qRT-PCR were equally applied to determine the expression of a set of proteins. The results showed that the expression level of mir-367 was decreased in the plasma of CAD patients compared with healthy controls while levels of NF-kappa B, IL-6 and TNF-alpha increased considerably. Kendall, Spearman and Pearson correlation analyses indicated that decreased mir-367 levels were significantly correlated with elevated levels of NF-kappa B, IL-6 and TNF-alpha. Receiver-operator curve (ROC) analysis showed the potential of mir-367 as a non-invasive biomarker for CAD diagnosis with an area under-curve (AUC) of 0.9697. Furthermore, in vitro studies showed that silencing of mir-367 in human aortic endothelial cells (HAECs) treated with oxLDL promoted the expression of NF-kappa B mediated inflammatory pathways while mir-367 mimic downregulated these pathways. Further analysis pointed to a role of mir-367 in the inhibition of NF-kappa B inflammatory pathways via negative regulation of EFR3A and upregulation of FBXW7, probably through the Akt/mTOR pathway. Conclusively, circulating mir-367 may be a new biomarker, a potential diagnostic tool and a candidate therapeutic target for CAD.

  • 出版日期2017
  • 单位济宁医学院