Portal de investigación
Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Burks, DJ
Grupos y Plataformas de I+D+i
Abstract
BackgroundType 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.MethodsA 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.ResultsAnalysis 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).ConclusionsDecreased 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.
© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated
Datos de la publicación
- ISSN/ISSNe:
- 1479-5876, 1479-5876
- Tipo:
- Article
- Páginas:
- 222-222
- PubMed:
- 31299986
Journal of Translational Medicine BIOMED CENTRAL LTD
Citas Recibidas en Web of Science: 15
Documentos
Filiaciones
Keywords
- Type 1 diabetes; Inflammation; Cardiovascular risk; T cells
Financiación
Proyectos y Estudios Clínicos
Papel de los procesos inflamatorios asociados a la diabetes en la estabilidad de la placa de ateroma y estudio del uso potencial de estrategias terapéuticas.
Investigador Principal: HERMINIA GONZÁLEZ NAVARRO
2016/109 . INSTITUTO SALUD CARLOS III . 2017
Cita
Martinez S,Sanchez V,Herrero A,Vinue A,Real JT,Ascaso JF,Burks DJ,Gonzalez H. Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes. J. Transl. Med. 2019. 17. (1):p. 222-222. IF:4,124. (2).
Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene expression in leukocytes. Martinez S, Sanchez V, Herrero A, Vinue A, Real JT, Ascaso JF, Burks DJ et al. Journal of Translational Medicine. 2019 julio 12. 17 (1):222-222. DOI:10.1186/s12967-019-1977-1. PMID:31299986.
