2026-07-22T20:05:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/96662024-09-27T09:55:47Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Purroy, Ana
author
Roncal, Carmen
author
Orbe, Josune
author
Meilhac, Olivier
author
Belzunce, Miriam
author
Zalba, Guillermo
author
Villa-Bellosta, Ricardo
author
Andres, Vicente
author
Parks, William C
author
Páramo, José A
author
Rodríguez, José A
funder
Ministerio de Educación y Ciencia (España)
funder
Ministerio de Sanidad y Consumo (España)
funder
Sociedad Española de Cardiología
funder
Sociedad Española de Arteriosclerosis
2020-04-21T14:24:06Z
2020-04-21T14:24:06Z
2018-11
Atherosclerosis. 2018; 278:124-134
10.1016/j.atherosclerosis.2018.09.022
1879-1484
00219150
Atherosclerosis
30268068
http://hdl.handle.net/20.500.12105/9666
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.
eng
Atherosclerosis
Calcification
Inflammation
Macrophage
Metalloproteinases
Matrix metalloproteinase-10 deficiency delays atherosclerosis progression and plaque calcification
journal article
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MatrixMetalloproteinase-10DeficiencyeDelays_2018.pdf
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MatrixMetalloproteinase-10DeficiencyeDelays_2018.pdf.txt