Synergistic Expression of Histone Deacetylase 9 and Matrix Metalloproteinase 12 in M4 Macrophages in Advanced Carotid Plaques

Oksala, Niku; Seppälä, Ilkka; Rahikainen, Rolle; Mäkelä, Kari-Matti; Raitoharju, Emma; Illig, Thomas; Klopp, Norman; Kholová, Ivana; Laaksonen, Reijo; Karhunen, P.J.; Hytönen, Vesa P.; Lehtimäki, Terho

doi:10.1016/j.ejvs.2017.02.014

Cited by 18 publications

(11 citation statements)

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“…Macrophages belong to a select group of cells that differentiate, go through phenotypic modification, and participate in the microbicidal response in the activation of the classical pathway by M1 macrophages or in tissue repair in response to the action of M2 macrophages [ 26 , 27 ]. Recently, the involvement of M4 macrophages in the pathogenesis of atherosclerosis has been recognized; however, the role of this new subtype in leprosy has not yet been investigated [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions

et al. 2018

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BackgroundSince macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy.MethodsWe analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry.ResultsThe M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection.ConclusionM4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions

et al. 2018

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“…Specifically, their exposure to CXCL4 was shown to lead to the production of CD68, IL-6, TNF-α, S100A8, MMP7, and MMP12. 136,137 M4 macrophages are highly enriched in atherosclerotic lesions, where the cells exhibit increased expression of LDL receptors. [138][139][140] This phenomenon causes accumulation of fat inside phagocytes, leading to the development of atheroma plaques and, consequently, oxidative lesions.…”

Section: Markers Of M1 M2 and M4 Macrophagesmentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.

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“…Histone modification in the cardiovascular system is an active field of research with growing evidence implicating a role of HDACs in the regulation of vessel homeostasis. Indeed, HDAC4 regulates vascular inflammation via activation of autophagy in endothelial cells ( 29 ) and the deletion of HDAC9 promotes inflammation resolution and reverse cholesterol transport in atherosclerosis and coronary heart diseases ( 30 , 31 ). In addition, elevation of acetyltransferase p300 accelerates aging ( 32 ).…”

Section: Epigenetic Mechanisms In Vascular Agingmentioning

confidence: 99%

Targeting Epigenetic Mechanisms in Vascular Aging

Lin

Ding

et al. 2022

Front. Cardiovasc. Med.

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Environment, diseases, lack of exercise, and aged tendency of population have becoming crucial factors that induce vascular aging. Vascular aging is unmodifiable risk factor for diseases like diabetes, hypertension, atherosclerosis, and hyperlipidemia. Effective interventions to combat this vascular function decline is becoming increasingly urgent as the rising hospitalization rate caused by vascular aging-related diseases. Fortunately, recent transformative omics approaches have enabled us to examine vascular aging mechanisms at unprecedented levels and precision, which make our understanding of slowing down or reversing vascular aging become possible. Epigenetic viz. DNA methylation, histone modifications, and non-coding RNA-based mechanisms, is a hallmark of vascular aging, its deregulation leads to aberrant transcription changes in tissues. Epigenetics mechanisms by mediating covalent modifications to DNA and histone proteins, consequently, influence the sensitivity and activities of signaling pathways in cells and tissues. A growing body of evidence supports correlations between epigenetic changes and vascular aging. In this article, we will provide a comprehensive overview of epigenetic changes associated with vascular aging based on the recent findings with a focus on molecular mechanisms of action, strategies to reverse epigenetic changes, and future perspectives.

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Synergistic Expression of Histone Deacetylase 9 and Matrix Metalloproteinase 12 in M4 Macrophages in Advanced Carotid Plaques

Abstract: M4 macrophages are a possible source for HDAC9 and MMP12 expression in advanced human plaques.

Cited by 18 publications

References 51 publications

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Targeting Epigenetic Mechanisms in Vascular Aging

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