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Type 1 diabetic mellitus patients with increased atherosclerosis risk display decreased CDKN2A/2B/2BAS gene
Sergio Martínez-Hervás1,2,3, Verónica Sánchez-García2, Andrea Herrero-Cervera2
1Endocrinology and Nutrition Department Hospital Clínico Universitario. Department of Medicine, University of Valencia, 46010, Valencia, Spain.
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 p16Ink4a), CDKN2A (p14Arf, variant 4), CDKN2B (p15Ink4b) 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.
Insights
Type 1 diabetes is linked to higher cardiovascular disease risk due to immune cell dysfunction. Lower CDKN2A/2B/2BAS gene expression in T1DM patients correlates with atherosclerosis markers and immune changes.
Area of Science:
- Immunology
- Endocrinology
- Cardiovascular Medicine
Background:
- Type 1 diabetes mellitus (T1DM) patients face elevated cardiovascular disease (CVD) risks.
- T1DM is associated with reduced regulatory T (Treg) cell function or numbers.
- Previous research links reduced CDKN2A/2B/2BAS gene expression to increased CVD risk.
Purpose of the Study:
- To investigate the relationship between CDKN2A/2B/2BAS gene expression, immune cell dysfunction, and cardiovascular risk in T1DM patients.
- To explore the potential role of CDKN2A/2B/2BAS genes in the pathogenesis of CVD in T1DM.
Main Methods:
- Cross-sectional study involving 90 subjects (controls and T1DM patients).
- Analysis of circulating leukocyte subpopulations via flow cytometry.
- Gene expression analysis (qPCR, Western blot) on peripheral blood mononuclear cells.
Main Results:
- T1DM patients exhibited decreased CD4+CD25+CD127- Treg cells and lower FOXP3, RORC, IL2, and IL6 mRNA levels.
- Reduced mRNA expression of CDKN2A (p16Ink4a, p14Arf), CDKN2B (p15Ink4b), and CDKN2BAS was observed in T1DM patients.
- T1DM patients showed increased pro-atherogenic CD14++CD16+ monocytes and enhanced common carotid intima-media thickness (CC-IMT).
Conclusions:
- Decreased CDKN2A/2B/2BAS expression in leukocytes is associated with increased CC-IMT and pro-atherogenic monocytes in T1DM.
- These findings suggest a potential role for CDKN2A/2B/2BAS genes in CVD risk among individuals with T1DM.
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