V Camarena1, D Sant1, M Mohseni2, T Salerno3, M L Zaleski2, G Wang4, G Iacobellis5. 1. John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, FL, USA. 2. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miami, FL, USA. 3. Department of Surgery, Division of Thoracic and Cardiac Surgery, University of Miami Miller School of Medicine, Miami, FL, USA. 4. John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, Miami, FL, USA. Electronic address: gwang@med.miami.edu. 5. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Miami, FL, USA. Electronic address: giacobellis@med.miami.edu.
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 AND RESULTS: 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.
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 AND RESULTS: 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.
Authors: Yu Xing Zhao; Hui Juan Zhu; Hui Pan; Xue Mei Liu; Lin Jie Wang; Hong Bo Yang; Nai Shi Li; Feng Ying Gong; Wei Sun; Yong Zeng Journal: Int J Endocrinol Date: 2019-08-25 Impact factor: 3.257
Authors: Lander Egaña-Gorroño; Raquel López-Díez; Gautham Yepuri; Lisa S Ramirez; Sergey Reverdatto; Paul F Gugger; Alexander Shekhtman; Ravichandran Ramasamy; Ann Marie Schmidt Journal: Front Cardiovasc Med Date: 2020-03-10