Coronary Heart Disease Fat Subcutaneous Fat And Non-differential Proteomics Epicardial Coronary Artery Disease In Patients With

Objective:Coronary artery disease (CAD) has already been great threaten to human health. Attributed to unique character of anatomical structure and metabolism, epicardial adipose tissue has attracted amount of attention. Recent researches suggested the volume of epicardial adipose from CAD patients was greater than non-CAD patients. Meanwhile, epicardial adipose tissue locally produced adipokines which may affect cardiovascular physiology and pathology. But researches on proteome of epicardial adipose tissue are rare and limited which adopted2DE-MS. With rapid development of proteomics techniques, the usage of iTRAQ and LC-MS/MS improves sensitivity of proteins identification greatly. Here, we aimed to study whether there were differences in proteome between epicardial and subcutaneous adipose tissue from patients with and without CAD by means of iTRAQ and LC-MS/MS to explore the possible mechanism of coronary artery atherosclerosis.Methods:Research subjects were patients from Peking Union Medical College Hospital. Epicardial adipose tissue and subcutaneous adipose tissue samples were collected from6CAD patients (M/F=4/2, age60.67±6.44) and6non-CAD patients (M/F=2/4, age49.0±7.51) undergoing heart surgery. There were no statistical differences in age, BMI, waist circumference, fasting blood glucose and blood lipid level (p>0.05).Total proteins of adipose tissue were extracted. Then we performed iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were analyzed by MASCOT and IPA (Ingenuity Pathway Analysis Software).Results:(1) There were totally2746proteins identified by LC-MS/MS. According to location in cells, the most proteins located in cytoplasm, then were nucleus and extracellular Space. According to types of proteins, the most were enzymes, and then were transporters and transmembrane receptors.(2) Compared to non-CAD patients,385differential proteins were found in epicardial adipose tissue which included214proteins up-regulated and171proteins down-regulated. The biological functions they involved in were cell to cell signaling and interaction, embryonic development, tissue development in sequence. The signal pathways they involved in including LXR/RXR activation, acute phase response signaling, and mitochondria dysfunction in sequence.(3)210differential proteins were found in subcutaneous adipose tissue which included71proteins up-regulated and139proteins down-regulated. The biological functions they involved in were embryonic development, hair and skin development, organ development in sequence. The signal pathways they involved in were LXR/RXR activation, ILK signaling and atherosclerosis signaling in sequence.(4) According to analysis of differential proteins from EAT and SAT, there were much more differential proteins in EAT from CAD patients involved in biological functions associated with CAD including cell-to-cell signaling and interaction, inflammatory response, metabolic disease, lipid metabolism, synthesis and metabolism of reactive oxygen species. Most of these differential proteins were up-regulated in epicardial adipose tissue but down-regulated in subcutaneous adipose tissue of CAD patients. Epicardial adipose tissue play positive role in above biological functions excluding lipid metabolism. In the analysis of differential proteins involved in pathways associated with CAD, epicardial adipose tissue mainly facilitated coronary heart disease through mitochondrial dysfunction, activation of NF-κB signaling pathway, inhibition of LXR/RXR activation signal pathway.Conclusion:(1) there were differential proteins between CAD patients and non-CAD patients no matter in EAT or SAT.(2) Some proteins in EAT may improve development of coronary artery atherosclerosis through taking part in cell-to-cell signaling and interaction, inflammatory response, metabolic disease, dysfunction of lipid metabolism, synthesis and metabolism of reactive oxygen species. In contrast, SAT may protect from development of atherosclerosis through inhibition these biological functions.(3) EAT may facilitate coronary heart disease through mitochondrial dysfunction, activation of NF-κB signaling pathway, inhibition of LXR/RXR activation signal pathway.