INFLAMMATION IN CORONARY ARTERY DISEASE (CAD): THE ROLE OF EPICARDIAL ADIPOSE TISSUE (EAT)

Introduction: Epicardial adipose tissue (EAT) has recently emerged as a new risk factor for coronary artery disease (CAD) since it was considered as an endocrine organ able to produce and release different adipokines involved in heart disorder due to its proximity to the myocardium. Elevated inflammatory infiltrate and cytokine production have been previously described in EAT from CAD patients and also few studies were focused on the reactive oxygen species (ROS) produced by EAT. Recently it has been also reported that toll-like receptors (TLRs) can be important mediators of adipose tissue inflammation by recognizing endogenous products released by damaged or dying cells. Because adipocyte death may be driven by hypertrophy, our aim was to study in CAD and non-CAD patients the adipocytes size of EAT in correlation with M1 or M2 macrophages tissue infiltration and TLR-2 and TLR-4 expression. Methods: EAT biopsies were collected from 30 CAD and 20 non-CAD patients. The EAT thickness was measured by echocardiography.The adipocytes size was determined by morphometric analysis. Microarray technology was used for gene expression analysis; macrophages phenotype and TLRs expression were analyzed by immunofluorescence and immunohistochemical tecniques. Chemokines levels were determined by immunoassays. ROS species were measured by electron paramagnetic resonance (EPR). Results: EAT of CAD patients showed higher local and circulating level of IL-18 and IL-15 that non-CAD patients and also higher expression of gene involved in white adipose tissue (WAT) involved in ROS production. EAT adipocytes were larger in CAD than non-CAD patients. EAT expression and production of the pro-inflammatory mediators MCP-1, PTX3, TNF-α, IL-6 as well as of TLR-2 and TLR-4 was higher in CAD than non-CAD patients. At the contrary, the expression of the anti-inflammatory adiponectin and perilipin A, a marker of adipocyte death, were reduced. In EAT from CAD we observed more CD68 positive cells which were also positive for TLR-2 and TLR-4. Macrophage phenotyping showed more CD11c+ cells in CAD than non-CAD patients and contrarily more CD206+ cells were present in non-CAD than CAD patients. Conclusions: our results suggested that EAT as a potential source of ROS species and pro-inflammatory mediators involved in CAD development like IL-18 and IL-15. Secondly we suggested also that the adipocyte hypertrophy in EAT of CAD patients may promote the increase of local tissue inflammation and adipocyte death.