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

Anusha N Seneviratne1, Jennifer E Cole2, Michael E Goddard2

  • 1Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom; Department of Bioengineering, Imperial College London, United Kingdom.

Insights

Low shear stress promotes pro-inflammatory macrophage (M1) programming in atherosclerosis. This study reveals shear stress as a key factor influencing macrophage polarization and plaque development in ApoE(-/-) mice.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Atherosclerosis Research

Background:

  • Macrophages are crucial in atherosclerotic plaques, exhibiting diverse polarization states (M1, M2, Mox, Mhem).
  • Previous work linked low (LSS) and oscillatory (OSS) shear stress to distinct plaque morphologies in ApoE(-/-) mice.

Purpose of the Study:

  • To investigate the relationship between varying shear stress conditions and macrophage polarization within atherosclerotic plaques.
  • To determine how shear stress influences plaque morphology in a mouse model of atherosclerosis.

Main Methods:

  • A shear stress-altering cast was applied to the carotid arteries of high-fat-fed ApoE(-/-) mice.
  • Macrophage polarization markers (iNOS, IRF5 for M1; Arginase-1, HO-1, CD163 for M2/Mox/Mhem) were analyzed in developing atherosclerotic lesions.

Main Results:

  • Low shear stress (LSS) lesions exhibited higher expression of M1 markers (iNOS, IRF5) compared to oscillatory shear stress (OSS) lesions.
  • OSS lesions showed elevated expression of M2/Mox/Mhem markers (Arginase-1, HO-1, CD163).

Conclusions:

  • Shear stress is a significant determinant of macrophage polarization in atherosclerosis.
  • Low shear stress conditions favor pro-inflammatory (M1) macrophage programming, contributing to specific plaque characteristics.