title: Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques.
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.
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom; Department of Bioengineering, Imperial College London, United Kingdom.
authors.forename: Anusha N
authors.initials: AN
authors.lastname: Seneviratne
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cole
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Goddard
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom.
authors.forename: Inhye
authors.initials: I
authors.lastname: Park
authors.affiliation: Department of Bioengineering, Imperial College London, United Kingdom.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mohri
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sansom
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom.
authors.forename: Irina
authors.initials: I
authors.lastname: Udalova
authors.affiliation: Department of Bioengineering, Imperial College London, United Kingdom.
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom. Electronic address: claudia.monaco@kennedy.ox.ac.uk.
authors.forename: Claudia
authors.initials: C
authors.lastname: Monaco
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D016764:Cell Polarity; D005260:Female; D008264:Macrophages / Q000473:pathology*; D008810:Mice, Inbred C57BL; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D033081:Shear Strength
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers
keywords: Atherosclerosis; Macrophage; Shear stress