DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues
| Autor: | Gallego-Fabrega C., Cullell N., Soriano-Tárraga C., Carrera C., Torres-Aguila N.P., Muiño E., Cárcel-Márquez J., de Moura M.C., Fernández-Sanlés A., Esteller M., Elosua R., Jiménez-Conde J., Roquer J., Montaner J., Krupinski J., Fernandez-Cadenas I. |
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| Rok vydání: | 2020 |
| Předmět: |
matrix metalloproteinase
hypertension phenotype carotid atherosclerosis DNA fingerprinting gene cluster Article smoking X chromosome blood controlled study human methyl CpG binding protein DNA extraction protein expression thrombosis DNA methylation genome-wide association study dyslipidemia stenosis gene mapping cohort analysis major clinical study brain ischemia human tissue DNA polymorphism tissue inhibitor of metalloproteinase CpG island gene expression blood sampling cerebrovascular accident carotid endarterectomy |
| Zdroj: | Oncotarget r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1949-2553 |
| Popis: | 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. © Copyright: Gallego-Fabrega et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Databáze: | OpenAIRE |
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