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

Anusha N Seneviratne, Jennifer Cole, Michael E Goddard, Inhye Park, Zahra Mohri, Stephen Sansom, Irina Udalova, Rob Krams, Claudia Monaco

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)168-72
Number of pages5
JournalJournal of molecular and cellular cardiology
Issue numberPt B
Publication statusPublished - Dec 2015
Externally publishedYes


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

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