CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7+S100A8+in vitro and in vivo

Erbel, Christian; Tyka, Mirjam; Helmes, Christian M.; Akhavanpoor, Mohammadreza; Rupp, Gregor; Sante, Gabriele Di; Linden, Fabian; Wolf, Anton; Doesch, Andreas O.; Lasitschka, Felix; Katus, Hugo A.; Gleissner, Christian A.

doi:10.1177/1753425914526461

Cited by 83 publications

(65 citation statements)

References 41 publications

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“…The mPTP comprises the voltage-dependent anion channel at the OMM and the adenine nucleotide translocase (ANT) and cyclophilin D (CypD) proteins at the IMM (42). Interestingly, Sloan et al showed that heart tissue from diabetic rats have more thiol oxidation when compared with nondiabetic animals (183), and thiol cross-linking agents such as diamide increase thiol oxidation of ANT at Cys 56 and cause mPTP opening (39).…”

Section: Mitochondrial Ros Associated With Protein-s-glutathionylationmentioning

confidence: 99%

“…Although the exact role of M1 and M2-polarized macrophages in atherosclerosis has yet to be defined, observational evidence suggests that the relative abundance of M1-polarized macrophages in lesions, in particular, in the unstable region of the plaque, that is, shoulder (19), is associated with plaque vulnerability [recently reviewed in Chinetti-Gbaguidi et al (33)]. More recently, an additional activation state of macrophages, termed M4 polarization, has been described, which is induced by platelet chemokine CXCL4, and demonstrates a unique transcriptome distinct from M1 and M2 polarization (56,74,75). M4-polarized macrophages, defined based on the coexpression of MMP-7 and S100A8, which seems to be exclusive to this activation state, have been identified in human coronary atherosclerotic plaques (56).…”

Section: Role Of Ros and Protein-s-glutathionylation In Monocyte Recrmentioning

confidence: 99%

“…More recently, an additional activation state of macrophages, termed M4 polarization, has been described, which is induced by platelet chemokine CXCL4, and demonstrates a unique transcriptome distinct from M1 and M2 polarization (56,74,75). M4-polarized macrophages, defined based on the coexpression of MMP-7 and S100A8, which seems to be exclusive to this activation state, have been identified in human coronary atherosclerotic plaques (56). Additionally, the abundance of M4-polarized macrophages, but not the CXCL4 plasma level, has been associated with plaque vulnerability (57).…”

Section: Role Of Ros and Protein-s-glutathionylation In Monocyte Recrmentioning

confidence: 99%

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Protein Thiol Redox Signaling in Monocytes and Macrophages

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Downs

Tavakoli

et al. 2016

Antioxidants & Redox Signaling

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Significance: Monocyte and macrophage dysfunction plays a critical role in a wide range of inflammatory disease processes, including obesity, impaired wound healing diabetic complications, and atherosclerosis. Emerging evidence suggests that the earliest events in monocyte or macrophage dysregulation include elevated reactive oxygen species production, thiol modifications, and disruption of redox-sensitive signaling pathways. This review focuses on the current state of research in thiol redox signaling in monocytes and macrophages, including (i) the molecular mechanisms by which reversible protein-S-glutathionylation occurs, (ii) the identification of bona fide S-glutathionylated proteins that occur under physiological conditions, and (iii) how disruptions of thiol redox signaling affect monocyte and macrophage functions and contribute to atherosclerosis. Recent Advances: Recent advances in redox biochemistry and biology as well as redox proteomic techniques have led to the identification of many new thiol redox-regulated proteins and pathways. In addition, major advances have been made in expanding the list of S-glutathionylated proteins and assessing the role that protein-S-glutathionylation and S-glutathionylation-regulating enzymes play in monocyte and macrophage functions, including monocyte transmigration, macrophage polarization, foam cell formation, and macrophage cell death. Critical Issues: Protein-S-glutathionylation/deglutathionylation in monocytes and macrophages has emerged as a new and important signaling paradigm, which provides a molecular basis for the well-established relationship between metabolic disorders, oxidative stress, and cardiovascular diseases. Future Directions: The identification of specific S-glutathionylated proteins as well as the mechanisms that control this post-translational protein modification in monocytes and macrophages will facilitate the development of new preventive and therapeutic strategies to combat atherosclerosis and other metabolic diseases. Antioxid. Redox Signal. 25,[816][817][818][819][820][821][822][823][824][825][826][827][828][829][830][831][832][833][834][835]

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Section: Mitochondrial Ros Associated With Protein-s-glutathionylationmentioning

confidence: 99%

Section: Role Of Ros and Protein-s-glutathionylation In Monocyte Recrmentioning

confidence: 99%

Section: Role Of Ros and Protein-s-glutathionylation In Monocyte Recrmentioning

confidence: 99%

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Protein Thiol Redox Signaling in Monocytes and Macrophages

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Downs

Tavakoli

et al. 2016

Antioxidants & Redox Signaling

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“…44 M4 macrophages can be found within human atherosclerotic plaques and are characterized by the expression of metalloproteinase 7 and the calcium binding protein S100A8. 50 Moreover, CXCL4-induced macrophages display a complete loss of atheroprotective CD163 expression, 51 which might result in a severe reduction in phagocytic capacity of this macrophage subset. Hence, M4 macrophages are assumed to be proinflammatory and proatherogenic.…”

Section: Chemokines Regulate the Fate Of Monocytes Within Atherosclermentioning

confidence: 99%

“…50 Moreover, CXCL4-induced macrophages display a complete loss of atheroprotective CD163 expression, 51 which might result in a severe reduction in phagocytic capacity of this macrophage subset. Hence, M4 macrophages are assumed to be proinflammatory and proatherogenic.…”

Section: Drechsler Et Al Monocytes In Atherosclerosis 1053mentioning

confidence: 99%

Chemokines Control Mobilization, Recruitment, and Fate of Monocytes in Atherosclerosis

Drechsler

Duchêne

Soehnlein

2015

ATVB

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Abstract-Atherosclerosis is a chronic inflammatory disease of large arteries and, among others, characterized by continuous influx of monocytes into the subendothelial space, subsequent macrophage accumulation, and foam cell formation. Chemokines and their receptors tightly orchestrate monocyte trafficking and fate from birth to death. This brief review summarizes our current understanding of the interplay between monocytes and chemokines entertaining crucial processes in atherosclerosis development, progression, and regression. Drechsler et al Monocytes in Atherosclerosis 1051contribute to arterial monocyte accumulation. Under steadystate conditions, classical monocyte homeostasis is tightly regulated by the CCL2/CCR2 axis and mice deficient for CCR2 display severely reduced counts of circulating classical monocytes. 12 Under acute inflammatory conditions, murine classical monocytes are mobilized from the bone marrow in a CCL2/ CCR2-and CCL7/CCR2-dependent fashion. 12,13 However, in the context of atherosclerosis, these axes seem to be of minor relevance as plasma concentrations of CCL2 and CCL7 do not increase in apolipoprotein E-deficient (Apoe −/− ) mice fed a high-fat diet. 6 Furthermore, although mice deficient of CCR2 display a markedly reduced number of circulating classical monocytes already under steady-state conditions, monocyte counts in these mice do still increase under hypercholesterolemia. 6 Instead, the CXCL1/CXCR2 axis has been unraveled to be of major importance in classical monocytosis induced by high-fat diet as plasma CXCL1 increases under such conditions and CXCL1 neutralization abrogates expansion of circulating classical monocytes.6 As a consequence, injection of CXCL1 neutralizing antibodies reduces lesional macrophage counts and resulting lesion sizes are smaller. 6Beside direct mobilization of classical monocytes from the bone marrow, a more recent study links cholesterol efflux via ATP-binding cassette transporters with hematopoietic stem and multipotential progenitor cell mobilization and extramedullary proliferation.14 This might be of high interest as the spleen has been identified as reservoir for classical monocytes, which can be readily mobilized during inflammation. 15 In accordance with this finding, splenectomized mice failed to develop a monocytosis under acute inflammatory conditions 15 and splenic monocytes give rise to lesional macrophages. 16 Of note, several chemokines, including CCL3 and CXCL8, have been shown to suppress hematopoietic stem and multipotential progenitor cell proliferation and may thus potentially counteract hematopoiesis under conditions of hypercholesterolemia. monocyte mobilization from sites of production, the lesion phenotype observed in CCR2-deficient mice may be ascribed to low circulating monocyte numbers rather than inhibited recruitment. 6The majority of chemotactic molecules is derived from circulating platelets and neutrophils or from tissue resident cells such as endothelial cells and macrophages. In fact, the importance of platelets in a...

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TRIM7 promotes proliferation and migration of vascular smooth muscle cells in atherosclerosis through activating c‐Jun/AP‐1

Zhang

et al. 2019

IUBMB Life

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Atherosclerosis (AS), with associated risk of stroke or cerebrovascular disease, is one of the most common causes of death globally. It has been well established that tripartite motif‐containing protein 7 Tripartite Motif‐containing 7 (Trim7), as an E3 ubiquitin protein ligase, is involved in protein ubiquitination and thus regulating cellular proliferation. Moreover, TRIM7 is upregulated in advanced carotid AS. However, the detailed mechanism of TRIM7 on regulation of AS remains unclear. In the present study, we firstly discovered that TRIM7 expression was robustly induced in platelet‐derived growth factor type BB‐treated vascular smooth muscle cells (VSMCs) and human atherosclerotic plaques. Functional approaches established that knockdown of TRIM7 inhibited proliferation and migration of VSMCs, as well as arrested the cell cycle at G1‐S, thus suppressing AS progression. Our results also identified that c‐Jun/activator protein 1 (AP‐1) signaling pathway was activated by TRIM7. Moreover, gain‐ and loss‐of‐function studies revealed that TRIM7 could promote proliferation and migration of VSMCs via activation of c‐Jun/AP‐1 signaling pathway. Finally, by using atherogenic apolipoprotein E‐deficient (apoE–/–) C57BL/6 mice with high‐fat diet AS model, we demonstrated that interference of TRIM7 could effectively mitigate in vivo AS via inactivation of c‐Jun/AP‐1 signaling pathway. In general, activation of c‐Jun/AP‐1 signaling pathway via TRIM7 could be an important mechanism in AS progression, thus shedding light on the development of novel therapeutics to the treatment of the disease.

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CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7⁺S100A8⁺in vitro and in vivo

Cited by 83 publications

References 41 publications

Protein Thiol Redox Signaling in Monocytes and Macrophages

Protein Thiol Redox Signaling in Monocytes and Macrophages

Chemokines Control Mobilization, Recruitment, and Fate of Monocytes in Atherosclerosis

TRIM7 promotes proliferation and migration of vascular smooth muscle cells in atherosclerosis through activating c‐Jun/AP‐1

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