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Updated: Mar 30, 2026

Implantation of a Carotid Cuff for Triggering Shear-stress Induced Atherosclerosis in Mice
Published on: January 13, 2012
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.
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.
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.
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