Macrophage polarization in atherosclerosis

Yang, Suping; Yuan, Hou-Qin; Yi, Hao; Zhong, Ren; Qu, Shun-Lin; Liu, Lu‐Shan; Wei, Dangheng; Tang, Zhi‐Han; Zhang, Jifeng; Jiang, Zhisheng

doi:10.1016/j.cca.2019.10.034

Cited by 139 publications

(116 citation statements)

References 38 publications

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“…Therefore, it is possible that the increase of M2 macrophages, stimulated by MLT, is necessary for reducing the atherosclerotic process. This hypothesis could be linked to the functions of these cells, which are related to anti-inflammatory expression markers, as reported by Yang et al [34]. To support this hypothesis, some researchers have shown that MLT ameliorates inflammation by suppressing the cells toward the pro-inflammatory M1 phenotype and circadian nuclear receptor.…”

Section: Discussionmentioning

confidence: 62%

Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments

Nardo

Rezzani

Facchetti

et al. 2020

IJMS

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Atherosclerosis represents one of the main risk factors for the development of cardiovascular diseases. Their etiologies have been studied in recent years in order to better define therapeutic targets for intervention and to identify diagnostic methods. Two different subtypes of macrophages, M1 and M2, have been described in physiological conditions. They can also be found in the atherosclerotic process, where they both have opposite roles in disease progression. Perivascular brown adipose tissue is also involved in inflammation and endothelial damage. In this work, we provide insights into the protective role of melatonin in the atherosclerotic process by morphological and 18F-FDG-PET/CT analyses. In particular, we examined the effects of melatonin on pathways that are linked to atherosclerosis development. We showed that melatonin, by suppressing M1 activity, reduced inflammation and directed macrophage polarization toward the M2 macrophage subtype. Moreover, melatonin preserved the activity of perivascular brown adipose tissue. In addition, 18F-FDG uptake is very high in mice treated with melatonin, confirming that other factors may alter 18F-FDG distribution. In conclusion, we showed that melatonin affects inflammatory pathways that have been linked to atherosclerosis, assessed the relationships of the 18F-FDG PET/CT parameters with macrophage markers and the production of their cytokines, which that have been defined by morphological evaluations.

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Section: Discussionmentioning

confidence: 62%

Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments

Nardo

Rezzani

Facchetti

et al. 2020

IJMS

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“…At the molecular level, chronic hyperlipidemia induces endothelial dysfunction and thus promotes deposition of cholesterol on the vascular wall [ 3 ]. Smooth muscle cells and macrophages uptake excess cholesterol then migrate into the middle layer of vessel wall, contributing to the formation of plaques [ 4 ]. Therefore, increased intake and decreased efflux of cholesterol from macrophages have been identified as a key contributor to macrophage dysfunction, which is associated with the development of AS [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidized LDL Disrupts Metabolism and Inhibits Macrophage Survival by Activating a miR-9/Drp1/Mitochondrial Fission Signaling Pathway

Xin

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Mitochondrial dysfunction is associated with macrophage damage, but the role of mitochondrial fission in macrophage cholesterol metabolism is not fully understood. In this study, we explored the influences of miR-9 and mitochondrial fission on macrophage viability and cholesterol metabolism. Macrophages were incubated with oxidized low-density lipoprotein (ox-LDL) in vitro, after which mitochondrial fission, cell viability, and cholesterol metabolism were examined using qPCR, ELISAs, and immunofluorescence. ox-LDL treatment significantly increased Drp1-associated mitochondrial fission. Transfection of Drp1 siRNA significantly reduced cell death, attenuated oxidative stress, and inhibited inflammatory responses in ox-LDL-treated macrophages. Interestingly, inhibition of Drp1-related mitochondrial fission also improved cholesterol metabolism by balancing the transcription of cholesterol influx/efflux enzymes. We also found that miR-9 was downregulated in ox-LDL-treated macrophages, and administration of a miR-9 mimic decreased Drp1 transcription and mitochondrial fission, as well as its effects. These results indicate that signaling via the novel miR-9/Drp1/mitochondrial fission axis is a key determinant of macrophage viability and cholesterol metabolism.

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“…MSCs are implicated in reducing the aggregation of TMϕ in the arterial intima (Shoji et al, 2011), inhibiting the formation of foam cells by elevating the number and function of Tregs in vivo (Wang et al, 2015) and by decreasing TNFα release (Li et al, 2015). All of these steps require regulation of TMϕ polarization and modulation of the phenotypes in the plaque (Yang et al, 2020). In this way, MSCs sense the inflammatory environment and attempt to mitigate TMϕ inflammatory responses.…”

Section: Metabolic Reprogramming Of Tmϕ By Mscsmentioning

confidence: 99%

Molecular Crosstalk Between Macrophages and Mesenchymal Stromal Cells

Stevens

Bowles

Yeago

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stromal cells (MSCs) have been widely investigated for regenerative medicine applications, from treating various inflammatory diseases as a cell therapy to generating engineered tissue constructs. Numerous studies have evaluated the potential effects of MSCs following therapeutic administration. By responding to their surrounding microenvironment, MSCs may mediate immunomodulatory effects through various mechanisms that directly (i.e., contact-dependent) or indirectly (i.e., paracrine activity) alter the physiology of endogenous cells in various disease pathologies. More specifically, a pivotal crosstalk between MSCs and tissue-resident macrophages and monocytes (TMφ) has been elucidated using in vitro and in vivo preclinical studies. An improved understanding of this crosstalk could help elucidate potential mechanisms of action (MOAs) of therapeutically administered MSCs. TMφ, by nature of their remarkable functional plasticity and prevalence within the body, are uniquely positioned as critical modulators of the immune system – not only in maintaining homeostasis but also during pathogenesis. This has prompted further exploration into the cellular and molecular alterations to TMφ mediated by MSCs. In vitro assays and in vivo preclinical trials have identified key interactions mediated by MSCs that polarize the responses of TMφ from a pro-inflammatory (i.e., classical activation) to a more anti-inflammatory/reparative (i.e., alternative activation) phenotype and function. In this review, we describe physiological and pathological TMφ functions in response to various stimuli and discuss the evidence that suggest specific mechanisms through which MSCs may modulate TMφ phenotypes and functions, including paracrine interactions (e.g., secretome and extracellular vesicles), nanotube-mediated intercellular exchange, bioenergetics, and engulfment by macrophages. Continued efforts to elucidate this pivotal crosstalk may offer an improved understanding of the immunomodulatory capacity of MSCs and inform the development and testing of potential MOAs to support the therapeutic use of MSCs and MSC-derived products in various diseases.

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Macrophage polarization in atherosclerosis

Cited by 139 publications

References 38 publications

Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments

Beneficial Effects of Melatonin on Apolipoprotein-E Knockout Mice by Morphological and 18F-FDG PET/CT Assessments

Oxidized LDL Disrupts Metabolism and Inhibits Macrophage Survival by Activating a miR-9/Drp1/Mitochondrial Fission Signaling Pathway

Molecular Crosstalk Between Macrophages and Mesenchymal Stromal Cells

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