DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
Gallego-Fabrega, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Cullell, Natalia (Institut d'Investigació Biomèdica Sant Pau)
Soriano-Tárraga, Carolina (Institut Hospital del Mar d'Investigacions Mèdiques)
Carrera, Caty (Institut d'Investigació Biomèdica Sant Pau)
Torres-Aguila, Nuria P.. (Institut d'Investigació Biomèdica Sant Pau)
Muiño, Elena (Institut d'Investigació Biomèdica Sant Pau)
Cárcel-Márquez, Jara (Institut d'Investigació Biomèdica Sant Pau)
de Moura, Manuel Castro (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Fernández-Sanlés, Alba (Institut Hospital del Mar d'Investigacions Mèdiques)
Esteller, M. (Institució Catalana de Recerca i Estudis Avançats)
Elosua, Roberto (Institut Hospital del Mar d'Investigacions Mèdiques)
Jiménez-Conde, Jordi (Institut Hospital del Mar d'Investigacions Mèdiques)
Roquer, Jaume (Institut Hospital del Mar d'Investigacions Mèdiques)
Montaner, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Krupinski, Jerzy
Fernandez-Cadenas, Israel (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	Background and Purpose: Polymorphisms and serum levels of Matrix Metalloproteinases (MMP) and Tissue Inhibitor of Metalloproteinases (TIMP) have been studied with regard to atheromatous plaques and ischemic stroke, while no studies of DNA methylation (DNAm) patterns of MMP or TIMP have been performed to that end. Here, we evaluate DNAm levels of the MMP and TIMP gene families in human carotid plaques and blood samples of atherothrombotic stroke patients. Methods: We profiled the DNAm status of stable and ulcerated atherosclerotic plaques obtained as pair sets from three patients who underwent carotid endarterectomy surgery. We selected 415 CpG sites, mapping into MMPs and TIMPs genes for further study. Secondly, the statistically associated CpG sites were analyzed in blood samples from two separate atherothrombotic stroke cohorts (total sample size = 307), ischemic stroke-cohort 1 (ISC-1): 37 atherothrombotic patients and 6 controls, ischemic stroke-cohort 2 (ISC-2): 80 atherothrombotic patients and 184 controls. DNAm levels from plaque tissue and blood samples were evaluated using a high-density microarray Infinium, HumanMethylation450 BeadChip and Infinium MethylationEPIC BeadChip. Results: Three CpG sites were statistically significantly associated with unstable plaque portions; cg02969624, q -value = 0. 035 (TIMP2), and cg04316754, q -value = 0. 037 (MMP24) were hypermethylated, while cg24211657 q -value = 0. 035 (TIMP2) was hypomethylated. Association of cg04316754 (MMP24) methylation levels with atherothrombotic risk was also observed in blood tissue: ISC-1 p -values = 0. 03, ISC-2 p -value = 1. 9 × 10 -04. Conclusions: The results suggest different DNAm status of MMP24 between stable and unstable atherothrombotic carotid plaques, and between atherothrombotic stroke and controls in blood samples.
Grants:	Instituto de Salud Carlos III CPII17-00021
Note:	Altres ajuts: This study was funded by the INVICTUS network, Generacion, Maestro EPIGENESIS, FEDER-ERDF, and BasicMar Regist projects from the Carlos III Health Institute, the AGAUR, the RecerCaixa 2013 and the European Regional Development Fund (ERDF). EPIGENESIS project (CarlosIII Institute, Marató TV3 and Fundació MútuaTerrassa).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Atherosclerotic plaque ; Epigenetics ; DNA methylation ; Matrix metalloproteinases
Published in:	Oncotarget, Vol. 11 (march 2020) , p. 905-912, ISSN 1949-2553

DOI: 10.18632/oncotarget.27469
PMID: 32206187

8 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles