دورية أكاديمية
Matrix metalloproteinase-10 deficiency delays atherosclerosis progression and plaque calcification
| العنوان: | Matrix metalloproteinase-10 deficiency delays atherosclerosis progression and plaque calcification |
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| المؤلفون: | Purroy, Ana, Roncal, Carmen, Orbe, Josune, Meilhac, Olivier, Belzunce, Miriam, Zalba, Guillermo, Villa-Bellosta, Ricardo, Andres, Vicente, Parks, William C, Páramo, José A, Rodríguez, José A |
| المساهمون: | Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Sociedad Española de Cardiología, Sociedad Española de Arteriosclerosis |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2018 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | Atherosclerosis, Calcification, Inflammation, Macrophage, Metalloproteinases, Aged, Animals, CD11b Antigen, Disease Progression, Endarterectomy, Carotid, Female, Gene Expression Profiling, Gene Expression Regulation, Enzymologic, Humans, Male, Matrix Metalloproteinase 10, Mice, Inbred C57BL, Knockout, ApoE, Middle Aged, Muscle, Smooth, Vascular, Plaque, Atherosclerotic, Vascular Calcification |
| الوصف: | BACKGROUND AND AIMS: Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis and vascular calcification. Among them, we reported that MMP10 is present in human atheroma, associated with atherosclerosis. However, it remains unclear whether MMP10 is involved in atherogenesis and vascular calcification. METHODS: MMP10 was measured in serum from patients with subclinical atherosclerosis and analyzed in carotid endarterectomies by immunostaining. ApoE-deficient mice (Apoe-/-) were crossed to MMP10-deficient (Mmp10-/-) mice and followed up to 20 months. Plaque area and composition were assessed by histology and immunohistochemistry. Inflammatory markers were measured in atherosclerotic plaques by RT-qPCR, and leukocyte subpopulations were analyzed by flow cytometry. In vitro calcification assays were performed in aortic vascular smooth muscle cells (VSMC). RESULTS: MMP10 serum levels were associated with coronary calcification in subjects with subclinical atherosclerosis. Immunostaining revealed MMP10 expression in human atheromas, spatially associated with calcification areas, and complicated plaques released higher amounts of MMP10 than non-diseased segments. Interestingly, vascular MMP10 expression was confined to the atherosclerotic lesion in Apoe-/- mice, and Apoe-/-Mmp10-/- showed a substantial reduction in atherosclerotic lesion size, macrophage content and plaque calcification. Reduced local and systemic inflammatory markers could be demonstrated in Apoe-/-Mmp10-/- by gene expression and flow cytometry analysis. Calcium phosphate deposition and vascular calcification markers were downregulated in VSMC from Apoe-/-Mmp10-/- mice. CONCLUSIONS: Delayed plaque progression and altered cellular composition in the absence of MMP10 suggests that MMP10 plays a role in atherosclerosis, favoring inflammation, development and complication of the plaque. ; Funded through the "UTE project CIMA" (University of Navarra), Ministerio de Educacion y Ciencia (SAF2009-12039, SAF2016-79151-R), Ministerio de Sanidad ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 00219150 1879-1484 |
| العلاقة: | https://doi.org/10.1016/j.atherosclerosis.2018.09.022Test; info:eu-repo/grantAgreement/ES/SAF2016-79151-R; SAF2009-12039; info:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2015). Modalidad proyectos en salud. (2015)/PI15/01807; info:fis/Instituto de Salud Carlos III/null/null/Subprograma de proyectos de investigacion en salud (AES 2014). Modalidad proyectos en salud. (2014)/PI14/01152; Atherosclerosis. 2018; 278:124-134; http://hdl.handle.net/20.500.12105/9666Test; Atherosclerosis |
| DOI: | 10.1016/j.atherosclerosis.2018.09.022 |
| الإتاحة: | https://doi.org/20.500.12105/9666Test https://doi.org/10.1016/j.atherosclerosis.2018.09.022Test https://hdl.handle.net/20.500.12105/9666Test |
| حقوق: | http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.56F2DC3F |
| قاعدة البيانات: | BASE |
| تدمد: | 00219150 18791484 |
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| DOI: | 10.1016/j.atherosclerosis.2018.09.022 |