Macrophage Subtypes in Symptomatic Carotid Artery and Femoral Artery Plaques

S, Shaikh; Brittenden, Julie; Lahiri, Raja; Brown, Paul A.J.; Thiès, Frank; Wilson, Heather M.

doi:10.1016/j.ejvs.2012.08.005

Cited by 87 publications

(75 citation statements)

References 24 publications

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“…Shaikh et al found a higher proportion of M1 proinflammatory macrophages and a reduced proportion of M2 cells in symptomatic carotid lesions (21). The discrepancy to our study could be due to the fact that the former study compared the ratio of macrophage subtypes in the carotid artery with those in vascular femoral plaques.…”

Section: Discussioncontrasting

confidence: 54%

Folate Receptor-β Imaging Using ^99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque

et al. 2014

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In atherosclerotic plaques, the risk of rupture is increased at sites of macrophage accumulation. Activated macrophages express folate receptor-β (FR-β), which can be targeted by folate coupled to radioactive ligands to visualize vulnerability. The aim of this study was to explore the presence of activated macrophages in human atherosclerotic plaques by 99m Tc-folate imaging and to evaluate whether this technique can discriminate between an M1-like and M2-like macrophage phenotype. Methods: Carotid endarterectomy specimens of 20 patients were incubated with 99m Tc-folate, imaged using micro-SPECT, and divided into 3-mm slices. The mean accumulation was calculated per slice, and the distribution of M1-like and M2-like macrophages per slice was quantified by immunohistochemical staining for CD86 as well as inducible nitric oxide synthase (iNOS) for M1 and CD163 and FR-β for M2 macrophages. Monocytes from healthy donors were differentiated toward M1-like or M2-like phenotype by in vitro culturing. Messenger RNA levels of specific M1 and M2 markers were measured by reversetranscription polymerase chain reaction and expression of FR-β, CD86, and CD163 by flow cytometry. Results: There was a heterogeneous accumulation of 99m Tc-folate in plaques (median, 2.45 [0.77-6.40] MBq/g). Slices with the highest 99m Tc-folate accumulation of each plaque showed significantly more expression of FR-β and CD163, compared with slices with the lowest 99m Tc-folate accumulation, which showed significantly more expression of iNOS. In in vitro polarized macrophages, messenger RNA expression of FR-β, mannose receptor, IL-10, and matrix metalloproteinase-9 was significantly increased in M2-like macrophages, compared with M1-like macrophages. On a receptor level, CD86 was shown to be overexpressed on M1-like macrophages whereas FR-β and CD163 were overexpressed on M2-like macrophages measured by flow cytometry. Conclusion: Higher numbers of M2-like macrophages were present in areas of high 99m Tc-folate accumulation than areas with low accumulation. It is anticipated that 99m Tcfolate imaging using SPECT as a marker for M2-like macrophages in atherosclerosis might be a good indicator for plaque vulnerability.

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Section: Discussioncontrasting

confidence: 54%

Folate Receptor-β Imaging Using ^99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque

et al. 2014

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“…The observed macrophage population was relatively more resistant to formation of foam cells and had increased ability to store engulfed cholesterol esters compared to M1 and resting macrophages. M1-specific markers were shown to be increased in carotid atherosclerotic lesions while M2 markers were preferentially located in femoral atherosclerotic plaques [41]. In addition, plaque M1 macrophages were shown to have up-regulated expression of several MMPs [42].…”

Section: Phenotypes Of Macrophages In Atherosclerotic Plaquesmentioning

confidence: 98%

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

Chistiakov

Bobryshev

Nikiforov

et al. 2015

International Journal of Cardiology

163

138

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“…M1 macrophages are considered more destructive, promoting the destabilisation and rupture of atherosclerotic plaques, whereas phagocytosis is more important in the role of M2 macrophages stimulating reparative processes, mediated by the production of anti-inflammatory cytokines and the suppression of pro-inflammatory signalling. 39 It has been suggested that 18 F-FDG and USPIO uptake may be able to differentiate these two distinct M1 and M2 macrophage sub-populations respectively. 40 In this study, the majority of 18 F-FDG uptake was identified in the shoulder region of the aneurysm, an area of high biomechanical stress, 41,42 with a particular tendency to rupture: perhaps related to a destructive macrophage phenotype in this area.…”

Section: Discussionmentioning

confidence: 99%

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms

McBride¹,

Joshi²,

Robson³

et al. 2016

Journal of Vascular Surgery

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WHAT THIS PAPER ADDSComparing these techniques identifies a modest correlation but some key differences related to the spatial distribution of 18 F-FDG and USPIO uptake. This may reflect the differing elements of macrophage activity detected by these modalities: glycolysis and phagocytosis. Further studies are needed to assess whether identification of this varying activity will influence aneurysm growth rates and the clinical outcome.Objectives: Inflammation is critical in the pathogenesis of abdominal aortic aneurysm (AAA) disease. Combined 18 F-fludeoxyglucose ( 18 F-FDG) positron emission tomography with computed tomography (PET-CT) and ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) are non-invasive methods of assessing tissue inflammation. The aim of this study was to compare these techniques in patients with AAA. Materials and methods: Fifteen patients with asymptomatic AAA with diameter 46 AE 7 mm underwent PET-CT with 18 F-FDG, and T2*-weighted MRI before and 24 hours after administration of USPIO. The PET-CT and MRI data were then co-registered. Standardised uptake values (SUVs) were calculated to measure 18 F-FDG activity, and USPIO uptake was determined using the change in R2*. Comparisons between the techniques were made using a quadrant analysis and a voxel-by-voxel evaluation. Results: When all areas of the aneurysm were evaluated, there was a modest correlation between the SUV on PET-CT and the change in R2* on USPIO-enhanced MRI (n ¼ 70,345 voxels; r ¼ .30; p < .0001). Although regions of increased 18 F-FDG and USPIO uptake co-localised on occasion, this was infrequent (kappa statistic 0.074; 95% CI 0.026e0.122).18 F-FDG activity was commonly focused in the shoulder region whereas USPIO uptake was more apparent in the main body of the aneurysm. Maximum SUV was lower in patients with mural USPIO uptake. Conclusions: Both 18 F-FDG PET-CT and USPIO-MRI uptake identify vascular inflammation associated with AAA. Although they demonstrate a modest correlation, there are distinct differences in the pattern and distribution of uptake, suggesting a differential detection of macrophage glycolytic and phagocytic activity respectively.

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Macrophage Subtypes in Symptomatic Carotid Artery and Femoral Artery Plaques

Abstract: Plaques from patients with recently symptomatic carotid disease have a predominance of M1-macrophages and higher lipid content than femoral plaques, consistent with a more unstable plaque.

Cited by 87 publications

References 24 publications

Folate Receptor-β Imaging Using ^99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque

Folate Receptor-β Imaging Using ^99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms

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Macrophage Subtypes in Symptomatic Carotid Artery and Femoral Artery Plaques

Abstract: Plaques from patients with recently symptomatic carotid disease have a predominance of M1-macrophages and higher lipid content than femoral plaques, consistent with a more unstable plaque.

Cited by 87 publications

References 24 publications

Folate Receptor-β Imaging Using 99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque

Folate Receptor-β Imaging Using 99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

Positron Emission Tomography and Magnetic Resonance Imaging of Cellular Inflammation in Patients with Abdominal Aortic Aneurysms

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Product

Resources

About

Folate Receptor-β Imaging Using ^99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque

Folate Receptor-β Imaging Using ^99mTc-Folate to Explore Distribution of Polarized Macrophage Populations in Human Atherosclerotic Plaque