c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells

Shikatani, Eric A.; Besla, Rickvinder; Ensan, Sherine; Upadhye, Aditi; Khyzha, Nadiya; Li, Angela; Emoto, Takuo; Chiu, Felix; Dégousée, Norbert; Moreau, Joshua M.; Perry, Heather M.; Thayaparan, Danya; Cheng, Henry S.; Pacheco, Shaun; Smyth, David; Noyan, Hossein; Zavitz, Caleb C. J.; Bauer, Carla M. T.; Hilgendorf, Ingo; Libby, Peter; Świrski, Filip K.; Gommerman, Jennifer L.; Fish, Jason E.; Stämpfli, Martin R.; Cybulsky, Myron I.; Rubin, Barry B.; Paige, Christopher J.; Bender, Timothy P.; McNamara, Coleen A.; Husain, Mansoor; Robbins, Clinton S.

doi:10.1016/j.celrep.2019.04.090

Cited by 4 publications

(5 citation statements)

References 41 publications

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“…4D) and extramedullary hematopoiesis in the spleen as previously described for Hem1 −/− mice (fig. S4G) (39). Although T cell numbers were unaltered in the spleen (fig.…”

Section: Hem1 −/− Mice Replicate Aberrant B Cell Development and Mult...mentioning

confidence: 93%

The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity

et al. 2020

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The WAVE regulatory complex (WRC) is crucial for assembly of the peripheral branched actin network constituting one of the main drivers of eukaryotic cell migration. Here, we uncover an essential role of the hematopoietic-specific WRC component HEM1 for immune cell development. Germline-encoded HEM1 deficiency underlies an inborn error of immunity with systemic autoimmunity, at cellular level marked by WRC destabilization, reduced filamentous actin, and failure to assemble lamellipodia. Hem1−/− mice display systemic autoimmunity, phenocopying the human disease. In the absence of Hem1, B cells become deprived of extracellular stimuli necessary to maintain the strength of B cell receptor signaling at a level permissive for survival of non-autoreactive B cells. This shifts the balance of B cell fate choices toward autoreactive B cells and thus autoimmunity.

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“…4D) and extramedullary hematopoiesis in the spleen as previously described for Hem1 −/− mice (fig. S4G) (39). Although T cell numbers were unaltered in the spleen (fig.…”

Section: Hem1 −/− Mice Replicate Aberrant B Cell Development and Mult...mentioning

confidence: 93%

The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity

et al. 2020

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“…Consistent with the results of the above studies, it has been shown that ferulic acid can increase the expression of MEF2C mRNA in mouse C2C12 myotubes (90) . As for the MYB, it has been shown that it exacerbates experimental atherosclerosis directly through its effects on B lymphocytes, limiting the levels of atheroprotective oxLDL- specific IgM antibodies (91) , while several human studies associate HNF1A polymorphisms with circulating CRP concentrations and CVD (92,93,94) . Importantly, in a subgroup representative of our entire study population, significant decreases in plasma levels of CRP and IL-6 were observed (5) , suggestive for cardiometabolic protective effects of mate extract and putative mediating role of HNF1A.…”

Section: Discussionmentioning

confidence: 99%

Multigenomic modifications in human circulating immune cells in response to consumption of polyphenol-rich extract of yerba mate (Ilex paraguariensis A. St.-Hil.) are suggestive of cardiometabolic protective effects

et al. 2022

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Mate is a traditional drink obtained from the leaves of yerba mate and rich in a diversity of plant bioactive compounds including polyphenols, particularly chlorogenic acids. Studies, even though limited, suggest that consumption of mate is associated with health effects, including prevention of cardiometabolic disorders. Molecular mechanisms underlying the potential health properties are still largely unknown, especially in humans. The aim of this study was to investigate nutrigenomic effects of mate consumption and identify regulatory networks potentially mediating cardiometabolic health benefits. Healthy middle-aged men at risk for cardiovascular disease consumed a standardized mate extract or placebo for 4 weeks. Global gene expression, including protein coding and non-coding RNAs profiles were determined using microarrays. Biological function analyses were performed using integrated bioinformatic tools. Comparison of global gene expression profiles showed significant change following mate consumption with 2635 significantly differentially expressed genes, among which 6 are miRNAs and 244 are lncRNAs. Functional analyses showed that these genes are involved in regulation of cell interactions and motility, inflammation or cell signaling. Transcription factors, such as MEF2A, MYB or HNF1A, could have their activity modulated by mate consumption either by direct interaction with polyphenol metabolites or by interactions of metabolites with cell signaling proteins, like p38 or ERK1/2, that could modulate transcription factor activity and regulate expression of genes observed. Correlation analysis suggests that expression profile is inversely associated with gene expression profiles of patients with cardiometabolic disorders. Therefore, mate consumption may exert cardiometabolic protective effects by modulating gene expression towards a protective profile.

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“…Mechanistically, THP-1 cells-derived EVs were shown to have an abundance of miRNA-150, which are transferred to human microvascular ECs-1 (HMECs-1), resulting in HMECs-1 migration by downregulating c-Myb (43). Notably, c-Myb, a nuclear transcription factor, was found to be highly expressed in atherosclerotic mice models and acted as a critical regulator of the atherosclerosis process (90). In addition, miRNA-21-3p and miRNA-142a-5p of EVs are secreted by macrophages.…”

Section: Monocytes/macrophagesmentioning

confidence: 99%

Mechanisms of Action of MiRNAs and LncRNAs in Extracellular Vesicle in Atherosclerosis

Liu

2021

Front. Cardiovasc. Med.

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Atherosclerosis, a complex chronic inflammatory disease, involves multiple alterations of diverse cells, including endothelial cells (ECs), vascular smooth muscle cells (VSMCs), monocytes, macrophages, dendritic cells (DCs), platelets, and even mesenchymal stem cells (MSCs). Globally, it is a common cause of morbidity as well as mortality. It leads to myocardial infarctions, stroke and disabling peripheral artery disease. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that secreted by multiple cell types and play a central role in cell-to-cell communication by delivering various bioactive cargos, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Emerging evidence demonstrated that miRNAs and lncRNAs in EVs are tightly associated with the initiation and development of atherosclerosis. In this review, we will outline and compile the cumulative roles of miRNAs and lncRNAs encapsulated in EVs derived from diverse cells in the progression of atherosclerosis. We also discuss intercellular communications via EVs. In addition, we focused on clinical applications and evaluation of miRNAs and lncRNAs in EVs as potential diagnostic biomarkers and therapeutic targets for atherosclerosis.

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c-Myb Exacerbates Atherosclerosis through Regulation of Protective IgM-Producing Antibody-Secreting Cells

Abstract: Highlights d Hypercholesterolemia increases c-Myb expression in the bone marrow d Reduced c-Myb activity attenuates atherosclerosis progression d c-Myb potentiates atherosclerosis directly through its effects on B lymphocytes d c-Myb limits atheroprotective IgM responses

Cited by 4 publications

References 41 publications

The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity

The cytoskeletal regulator HEM1 governs B cell development and prevents autoimmunity

Multigenomic modifications in human circulating immune cells in response to consumption of polyphenol-rich extract of yerba mate (Ilex paraguariensis A. St.-Hil.) are suggestive of cardiometabolic protective effects

Mechanisms of Action of MiRNAs and LncRNAs in Extracellular Vesicle in Atherosclerosis

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