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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 (Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain)
Fernández-Sanlés, Alba (Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Barcelona, Spain)
Esteller, Manel (Institucio Catalana de Recerca i Estudis Avançats, Barcelona, Spain)
Elosua, Roberto (Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute, Universitat Pompeu Fabra, Barcelona, Spain)
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 (* These authors contributed equally to this work)
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.
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).
Note: Número d'acord de subvenció ISCIII/CPII17-00021
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. Creative Commons
Language: Anglès
Document: article ; recerca ; publishedVersion
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

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2020-07-13, last modified 2020-11-09

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