Matrix metalloproteinase-10 deficiency delays atherosclerosis progression and plaque calcification
| Autor: | William C. Parks, Ana Purroy, Vicente Andrés, Carmen Roncal, Olivier Meilhac, José A. Páramo, M. Belzunce, Jose A. Rodriguez, Josune Orbe, Ricardo Villa-Bellosta, Guillermo Zalba |
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| Přispěvatelé: | Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Sociedad Española de Cardiología, Sociedad Española de Arteriosclerosis |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Vascular smooth muscle Macrophage Mice Knockout ApoE Inflammation 030204 cardiovascular system & hematology Matrix metalloproteinase Gene Expression Regulation Enzymologic Muscle Smooth Vascular Calcification Lesion 03 medical and health sciences Mice 0302 clinical medicine Matrix Metalloproteinase 10 medicine Animals Humans Vascular Calcification Aged Endarterectomy Carotid CD11b Antigen business.industry Gene Expression Profiling Middle Aged medicine.disease Atherosclerosis Metalloproteinases Plaque Atherosclerotic Mice Inbred C57BL 030104 developmental biology Atheroma Disease Progression Female medicine.symptom Cardiology and Cardiovascular Medicine business Immunostaining |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) |
| Popis: | 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 y Consumo (PI14/01152 and PI15/01807), Sociedad Espanola de Cardiologia, Sociedad Espanola de Arteriosclerosis, Red de Investigacion Cardiovascular RIC (RD12/0042/0009), the gs5: Fondation pour la Recherche Medicale and the Fondation de France. Sí |
| Databáze: | OpenAIRE |
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