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Title: DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
Author: Gallego Fàbrega, Cristina
Cullell, Natalia
Soriano Tarraga, Carolina
Carrera, Caty
Torres Águila, Nuria Paz
Muiño, Elena
Cárcel Márquez, Jara
Castro de Moura, Manuel
Fernández Sanles, Alba
Esteller, Manel
Elosua, Roberto
Jiménez Conde, Jordi
Roquer, Jaume
Montaner, Joan
Krupinski, Jerzy
Fernández Cadenas, Israel
Keywords: ADN
Issue Date: 10-Mar-2020
Publisher: Impact Journals
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.
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It is part of: Oncotarget, 2020, vol. 11, num. 10, p. 905-912
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ISSN: 1949-2553
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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