Background Hypertrophy of epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) as in obesity is associated with several cardiac risk factors and higher carotid intima-media thickness, suggesting a pathogenic role of both cardiac fat tissue in the development of atherosclerosis. Curbing epicardial and pericardial adipose tissue dysmetabolism and associated inflammation may represent a novel therapeutic target to prevent coronary atherosclerosis.
Purpose Evaluate pro-atherogenic properties of EAT and PAT, development a feasible method for isolation of adipocytes and evaluate the adipocyte response to therapeutics and micronutrients.
Methods EAT and PAT were collected from coronary patients undergoing CABG (coronary patients) and from patients undergoing aortic or mitral valve surgery (valvular patients). Basal tissue expression of pro-inflammatory and pro-atherogenic genes was evaluated by rt-PCR. Then adipocytes were isolated and characterized. Finally, we tested the adipocyte ability to challenge vascular endothelium end their responsivity to cytokines and to the cardio-protective nutraceutical docosahexaenoic acid(DHA).
Results Basal expression of inflammatory genes in adipose samples was higher in coronary patients than in valvular patients. Adipocytes isolated from these fat pads were pure and can be sub-cultured for several days without losing viability and retaining the ability to respond to pro-inflammatory stimuli. Concordantly, their secretome was able to “inflammate” vascular endothelial cells and sustain the recruitment and adhesion of monocyte to endothelial surface. On the other hand, the exposure of adipocytes to DHA resulted in a downregulation of MCP-1, CXCL10, IL-6 and MMP-9 expression( 0.05) and in the upregulation of metabolic gene UCP-1 and -2 and PPARγ( 0.05) while leaving unaffected the expression of adiponectin.
Conclusion(s) Our data confirm the proatherogenic role of EAT in determining coronary atherosclerosis and suggests a similar pathogenic role for PAT. Furthermore, we propose a new efficient method for isolating adipocytes from PAT, obtaining cells that can be used as a potential bioreactor to test the response of adipose tissues to drugs and nutraceuticals.