Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques

J Mol Cell Cardiol. 2015 Dec;89(Pt B):168-72. doi: 10.1016/j.yjmcc.2015.10.034. Epub 2015 Oct 30.

Abstract

Macrophages, a significant component of atherosclerotic plaques vulnerable to acute complications, can be pro-inflammatory (designated M1), regulatory (M2), lipid- (Mox) or Heme-induced (Mhem). We showed previously that low (LSS) and oscillatory (OSS) shear stress cause thin-cap fibroatheroma and stable smooth muscle cell-rich plaque formation respectively in ApoE-knockout (ApoE(-/-)) mice. Here we investigated whether different shear stress conditions relate to specific changes in macrophage polarization and plaque morphology by applying a shear stress-altering cast to the carotid arteries of high fat-fed ApoE(-/-) mice. The M1 markers iNOS and IRF5 were highly expressed in macrophage-rich areas of LSS lesions compared to OSS lesions 6weeks after cast placement, while the M2 marker Arginase-1, and Mox/Mhem markers HO-1 and CD163 were elevated in OSS lesions. Our data indicates shear stress could be an important determinant of macrophage polarization in atherosclerosis, with low shear promoting M1 programming.

Keywords: Atherosclerosis; Macrophage; Shear stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / metabolism
  • Biomarkers / metabolism
  • Carotid Arteries / pathology
  • Cell Polarity*
  • Female
  • Macrophages / pathology*
  • Mice, Inbred C57BL
  • Plaque, Atherosclerotic / pathology*
  • Shear Strength*

Substances

  • Apolipoproteins E
  • Biomarkers