Tnfaip2 promotes atherogenesis by enhancing oxidative stress induced inflammation

Mol Immunol. 2022 Nov:151:41-51. doi: 10.1016/j.molimm.2022.08.019. Epub 2022 Sep 6.

Abstract

The inflammation is considered to be the crucial determinants of lesion progression and plaque stability during atherogenesis. Tnfaip2 appears to be a regulator for carcinogenesis and infectious diseases. But its role in atherosclerosis is not clear. Here we first report that Tnfaip2 promotes the formation of atherosclerosis through enhancing the inflammation under oxidative stress condition. Although the endogenous expression of Tnfaip2 was upregulated under oxidative stress condition, the overexpressed Tnfaip2 could promote cells proliferation. This might result from the ability of promoting cells entering G2/M phase. Conversely, the cells proliferation and migration were significantly reduced in Tnfaip2 knockdown cells through inhibiting the activation of NF-κB/MAPK/Akt signaling pathways. However, the efferocytosis increased markedly due to the upregulation of "eat me" receptors, such as CD36, SR-A, and SR-B1, and the downregulation of "don't eat me" signal CD47. As a consequence, Tnfaip2 deficiency in bone marrow-derived cells inhibited atherosclerosis development in Ldlr-/- mice fed a high-fat diet accompanied by decreased inflammatory cytokines and shTnfaip2 could reduce the plaque lesions in ApoE-/- mice. These results indicate that Tnfaip2 might play an important role during atherogenesis.

Keywords: Atherogenesis; Efferocytosis; Inflammation; Oxidative stress; Tnfaip2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / metabolism
  • Atherosclerosis* / genetics
  • Atherosclerosis* / metabolism
  • CD47 Antigen
  • Cytokines / metabolism
  • Inflammation
  • Mice
  • NF-kappa B / metabolism
  • Oxidative Stress
  • Plaque, Atherosclerotic* / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Tumor Necrosis Factors / metabolism*

Substances

  • Apolipoproteins E
  • CD47 Antigen
  • Cytokines
  • M-sec protein, mouse
  • NF-kappa B
  • Tumor Necrosis Factors
  • Proto-Oncogene Proteins c-akt