Novel atherogenic pathways from the differential transcriptome analysis of diabetic epicardial adipose tissue.
Nutr Metab Cardiovasc Dis
; 27(8): 739-750, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28739185
ABSTRACT
BACKGROUND AND AIM:
To evaluate the epicardial adipose tissue (EAT) transcriptome in comparison to subcutaneous fat (SAT) in coronary artery disease (CAD) and type 2 diabetes (T2DM). METHODS ANDRESULTS:
SAT and EAT samples were obtained from subjects with T2DM and CAD (n = 5) and those without CAD with or without T2DM (=3) undergoing elective cardiac surgery. RNA-sequencing analysis was performed in both EAT and SAT. Gene enrichment analysis was conducted to identify pathways affected by the differentially expressed genes. Changes of top genes were verified by quantitative RT-PCR (qRT-PCR), western blot, and immunofluorescence. A total of 592 genes were differentially expressed in diabetic EAT, whereas there was no obvious changes in SAT transcriptome between diabetics and non-diabetics. Diabetic EAT was mainly enriched in inflammatory genes, such as Colony Stimulating Factor 3 (CSF3), Interleukin-1b (IL-1b), IL-6. KEGG pathway analysis confirmed that upregulated genes were involved in inflammatory pathways, such as Tumor Necrosis Factor (TNF), Nuclear Factor-κB (NF-κB) and advanced glycation end-products-receptor advanced glycation end products (AGE-RAGE). The overexpression of inflammatory genes in diabetic EAT was largely correlated with upregulated transcription factors such as NF-κB and FOS.CONCLUSIONS:
Diabetic EAT transcriptome is significantly different when compared to diabetic SAT and highly enriched with genes involved in innate immune response and endothelium, like Pentraxin3 (PTX3) and Endothelial lipase G (LIPG). EAT inflammatory genes expression could be induced by upregulated transcription factors, mainly NF-kB and FOSL, primarily activated by the overexpressed AGE-RAGE signaling. This suggests a unique and novel atherogenic pathway in diabetes.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pericardium
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Coronary Artery Disease
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Adipose Tissue
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Gene Expression Profiling
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Diabetes Mellitus, Type 2
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Diabetic Angiopathies
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Atherosclerosis
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Transcriptome
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Inflammation
Type of study:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Aged
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Nutr Metab Cardiovasc Dis
Year:
2017
Document type:
Article