Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis
Abstract Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progre...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-07-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201607492 |
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| author | Alberto Canfrán‐Duque Noemi Rotllan Xinbo Zhang Marta Fernández‐Fuertes Cristina Ramírez‐Hidalgo Elisa Araldi Lidia Daimiel Rebeca Busto Carlos Fernández‐Hernando Yajaira Suárez |
| author_facet | Alberto Canfrán‐Duque Noemi Rotllan Xinbo Zhang Marta Fernández‐Fuertes Cristina Ramírez‐Hidalgo Elisa Araldi Lidia Daimiel Rebeca Busto Carlos Fernández‐Hernando Yajaira Suárez |
| author_sort | Alberto Canfrán‐Duque |
| collection | DOAJ |
| description | Abstract Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. Here, we define the contribution of miR‐21 in hematopoietic cells during atherogenesis. Interestingly, we found that miR‐21 is the most abundant miRNA in macrophages and its absence results in accelerated atherosclerosis, plaque necrosis, and vascular inflammation. miR‐21 expression influences foam cell formation, sensitivity to ER‐stress‐induced apoptosis, and phagocytic clearance capacity. Mechanistically, we discovered that the absence of miR‐21 in macrophages increases the expression of the miR‐21 target gene, MKK3, promoting the induction of p38‐CHOP and JNK signaling. Both pathways enhance macrophage apoptosis and promote the post‐translational degradation of ABCG1, a transporter that regulates cholesterol efflux in macrophages. Altogether, these findings reveal a major role for hematopoietic miR‐21 in atherogenesis. |
| format | Article |
| id | doaj-art-9c10e68c45eb4231aed7f8eaef9ae744 |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2017-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-9c10e68c45eb4231aed7f8eaef9ae7442025-08-20T03:46:13ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-07-01991244126210.15252/emmm.201607492Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesisAlberto Canfrán‐Duque0Noemi Rotllan1Xinbo Zhang2Marta Fernández‐Fuertes3Cristina Ramírez‐Hidalgo4Elisa Araldi5Lidia Daimiel6Rebeca Busto7Carlos Fernández‐Hernando8Yajaira Suárez9Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineServicio de Bioquímica‐Investigación, Hospital Universitario Ramón y Cajal de Investigación Sanitaria (IRyCIS)Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program and the Departments of Comparative Medicine and Pathology, Yale University School of MedicineAbstract Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. Here, we define the contribution of miR‐21 in hematopoietic cells during atherogenesis. Interestingly, we found that miR‐21 is the most abundant miRNA in macrophages and its absence results in accelerated atherosclerosis, plaque necrosis, and vascular inflammation. miR‐21 expression influences foam cell formation, sensitivity to ER‐stress‐induced apoptosis, and phagocytic clearance capacity. Mechanistically, we discovered that the absence of miR‐21 in macrophages increases the expression of the miR‐21 target gene, MKK3, promoting the induction of p38‐CHOP and JNK signaling. Both pathways enhance macrophage apoptosis and promote the post‐translational degradation of ABCG1, a transporter that regulates cholesterol efflux in macrophages. Altogether, these findings reveal a major role for hematopoietic miR‐21 in atherogenesis.https://doi.org/10.15252/emmm.201607492apoptosisatherosclerosismacrophage polarizationmiRNA |
| spellingShingle | Alberto Canfrán‐Duque Noemi Rotllan Xinbo Zhang Marta Fernández‐Fuertes Cristina Ramírez‐Hidalgo Elisa Araldi Lidia Daimiel Rebeca Busto Carlos Fernández‐Hernando Yajaira Suárez Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis EMBO Molecular Medicine apoptosis atherosclerosis macrophage polarization miRNA |
| title | Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis |
| title_full | Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis |
| title_fullStr | Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis |
| title_full_unstemmed | Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis |
| title_short | Macrophage deficiency of miR‐21 promotes apoptosis, plaque necrosis, and vascular inflammation during atherogenesis |
| title_sort | macrophage deficiency of mir 21 promotes apoptosis plaque necrosis and vascular inflammation during atherogenesis |
| topic | apoptosis atherosclerosis macrophage polarization miRNA |
| url | https://doi.org/10.15252/emmm.201607492 |
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