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Open Access 01-12-2019 | Arterial Occlusive Disease | Research

Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes

Authors: Sergio Martínez-Hervás, Verónica Sánchez-García, Andrea Herrero-Cervera, Ángela Vinué, José Tomás Real, Juan F. Ascaso, Deborah Jane Burks, Herminia González-Navarro

Published in: Journal of Translational Medicine | Issue 1/2019

Abstract

Background

Type 1 diabetes mellitus (T1DM) patients display increased risk of cardiovascular disease (CVD) and are characterized by a diminished regulatory T (Treg) cell content or function. Previous studies have shown an association between decreased CDKN2A/2B/2BAS gene expression and enhanced CVD. In the present study the potential relationship between CDKN2A/2B/2BAS gene expression, immune cell dysfunction and increased cardiovascular risk in T1DM patients was explored.

Methods

A cross-sectional study was performed in 90 subjects divided into controls and T1DM patients. Circulating leukocyte subpopulations analysis by flow cytometry, expression studies on peripheral blood mononuclear cell by qPCR and western blot and correlation studies were performed in both groups of subjects.

Results

Analysis indicated that, consistent with the described T cell dysfunction, T1DM subjects showed decreased circulating CD4+CD25+CD127− Treg cells. In addition, T1DM subjects had lower mRNA levels of the transcription factors FOXP3 and RORC and lower levels of IL2 and IL6 which are involved in Treg and Th17 cell differentiation, respectively. T1DM patients also exhibited decreased mRNA levels of CDKN2A (variant 1 p16^Ink4a), CDKN2A (p14^Arf, variant 4), CDKN2B (p15^Ink4b) and CDKN2BAS compared with controls. Notably, T1DM patients had augmented pro-atherogenic CD14++CD16+-monocytes, which predict cardiovascular acute events and enhanced common carotid intima-media thickness (CC-IMT).

Conclusions

Decreased expression of CDKN2A/2B/2BAS in leukocytes associates with increased CC-IMT atherosclerosis surrogate marker and proatherogenic CD14++CD16+ monocytes in T1DM patients. These results suggest a potential role of CDKN2A/2B/2BAS genes in CVD risk in T1DM.

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Title: Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes
Authors: Sergio Martínez-Hervás
Verónica Sánchez-García
Andrea Herrero-Cervera
Ángela Vinué
José Tomás Real
Juan F. Ascaso
Deborah Jane Burks
Herminia González-Navarro
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Arterial Occlusive Disease
Type 1 Diabetes
Published in: Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-019-1977-1

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Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes

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Conclusions

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Abstract

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