Low shear stress induces M1 macrophage polarization in murine thin-cap atherosclerotic plaques. (December 2015)

• Record Type: Journal Article
• Authors: Seneviratne, Anusha N.; Cole, Jennifer E.; Goddard, Michael E.; Park, Inhye; Mohri, Zahra; Sansom, Stephen; Udalova, Irina; Krams, Rob; Monaco, Claudia
• Is Part Of: Journal of molecular and cellular cardiology. Volume 89:Part B(2015)
• Page Start: 168
• Page End: 172
• Publication Date: 2015-12
• Subjects: ApoE−/− apolipoprotein E knockout -- HO-1 heme oxygenase-1 -- IL-4 interleukin 4 -- IL-10 interleukin 10 -- IL-12 interleukin 12 -- IL-13 interleukin 13 -- IFN-γ interferon gamma -- iNOS inducible nitric oxide synthase -- IRF5 interferon regulatory factor 5 -- LSS low shear stress -- 8-HG 8-hydroxyguanosine -- OSS oscillatory shear stress -- TCFA thin-cap fibroatheroma -- Th1 T helper 1 -- TNF-α tumor necrosis factor alpha; Atherosclerosis -- Macrophage -- Shear stress; Cardiology -- Periodicals; Heart Diseases -- Periodicals; Molecular Biology -- Periodicals; Cardiologie -- Périodiques; Cardiology; Electronic journals; Periodicals; 616.12
• DOI: 10.1016/j.yjmcc.2015.10.034
• Languages: English
• ISSNs: 0022-2828

Abstract

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 6 weeks 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.