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Map3k8 Modulates Monocyte State and Atherogenesis in ApoE¿/¿ Mice

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Sanz Garcia, Carlos & Sánchez, Ángela & Contreras Jurado, Silvia Constanza & Cales, Carmela & Barranquero, Cristina & Muñoz, Marta & Merino, Ramón & Escudero, Paula & Sanz, Maria Jesús & Osada, Jesús & Aranda, Ana & Alemany, Susana .Map3k8 Modulates Monocyte State and Atherogenesis in ApoE¿/¿ Mice.

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Sanz Garcia, Carlos & Sánchez, Ángela & Contreras Jurado, Silvia Constanza & Cales, Carmela & Barranquero, Cristina & Muñoz, Marta & Merino, Ramón & Escudero, Paula & Sanz, Maria Jesús & Osada, Jesús & Aranda, Ana & Alemany, Susana. Map3k8 Modulates Monocyte State and Atherogenesis in ApoE¿/¿ Mice.

https://hdl.handle.net/20.500.12080/26191
dc.contributor.author Sanz Garcia, Carlos
dc.contributor.author Sánchez, Ángela
dc.contributor.author Contreras Jurado, Silvia Constanza
dc.contributor.author Cales, Carmela
dc.contributor.author Barranquero, Cristina
dc.contributor.author Muñoz, Marta
dc.contributor.author Merino, Ramón
dc.contributor.author Escudero, Paula
dc.contributor.author Sanz, Maria Jesús
dc.contributor.author Osada, Jesús
dc.contributor.author Aranda, Ana
dc.contributor.author Alemany, Susana
dc.date.accessioned 2021-11-10T17:22:25Z
dc.date.available 2021-11-10T17:22:25Z
dc.date.created 2017-02
dc.identifier.uri https://hdl.handle.net/20.500.12080/26191
dc.description.abstract OBJECTIVE¿ Map3k8 (Cot/Tpl2) activates the MKK1/2-ERK1/2, MAPK pathway downstream from interleukin-1R, tumor necrosis factor-¿R, NOD-2R (nucleotide-binding oligomerization domain-like 2R), adiponectinR, and Toll-like receptors. Map3k8 plays a key role in innate and adaptive immunity and influences inflammatory processes by modulating the functions of different cell types. However, its role in atherogenesis remains unknown. In this study, we analyzed the role of this kinase in this pathology. APPROACH AND RESULTS¿ We show here that Map3k8 deficiency results in smaller numbers of Ly6ChighCD11clow and Ly6ClowCD11chigh monocytes in ApoE¿/¿ mice fed a high-fat diet (HFD). Map3k8¿/¿ApoE¿/¿ monocytes displayed high rates of apoptosis and reduced amounts of Nr4a1, a transcription factor known to modulate apoptosis in Ly6ClowCD11chigh monocytes. Map3k8¿/¿ApoE¿/¿ splenocytes and macrophages showed irregular patterns of cytokine and chemokine expression. Map3k8 deficiency altered cell adhesion and migration in vivo and decreased CCR2 expression, a determinant chemokine receptor for monocyte mobilization, on circulating Ly6ChighCD11clow monocytes. Map3k8¿/¿ApoE¿/¿ mice fed an HFD showed decreased cellular infiltration in the atherosclerotic plaque, with low lipid content. Lesions had similar size after Map3k8+/+ApoE¿/¿ bone marrow transplant into Map3k8¿/¿ApoE¿/¿ and Map3k8+/+ApoE¿/¿ mice fed an HFD, whereas smaller plaques were observed after the transplantation of bone marrow lacking both ApoE and Map3k8. CONCLUSIONS¿ Map3k8 decreases apoptosis of monocytes and enhances CCR2 expression on Ly6ChighCD11clow monocytes of ApoE¿/¿ mice fed an HFD. These findings explain the smaller aortic lesions in ApoE¿/¿ mice with Map3k8¿/¿ApoE¿/¿ bone marrow cells fed an HFD, supporting further studies of Map3k8 as an antiatherosclerotic target. es_ES
dc.format application/pdf es_ES
dc.language eng es_ES
dc.rights CC-BY es_ES
dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.es es_ES
dc.subject apoptosis ¿ atherosclerosis ¿ bone marrow ¿ monocytes ¿ Toll-like receptors es_ES
dc.title Map3k8 Modulates Monocyte State and Atherogenesis in ApoE¿/¿ Mice es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


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