Inflammasome activation in epicardial, pericardial and subcutaneous adipose tissue in patients with coronary heart disease

Abstract

Abstract Background The adipose tissue (AT) compartments surrounding the heart have been claimed to exert different pro-inflammatory properties with different associations with cardiovascular disease states. The epicardial AT (EAT), located close to the coronary arteries between the myocardium and the pericardial layer, seems to be associated with atherosclerosis and metabolic syndrome, whereas the pericardial AT (PAT), separated from the heart by the pericardium, is discussed to have less pro-inflammatory properties. Purpose The aim of the present study was to explore any differences in genetic regulation of pro-inflammatory markers included in the inflammasome related pathway in EAT, PAT and in subcutaneous AT (SAT). In addition, any relationship to the corresponding inflammatory markers in the circulation was explored. Materials and methods Biopsies from EAT, PAT and SAT, and arterial blood samples were collected from 52 patients with coronary heart disease (CHD) undergoing coronary by-pass surgery (aged 48–82 years, 70% male, median body mass index (BMI) 27.3 kg/m2). RNA was extracted by use of RNeasy Lipid Tissue Mini Kits. Gene expression of Interleukin (IL)-1β, IL-18, NLRP3, Caspase-1, toll-like receptor 4 (TLR4), IL-6, IL-6 receptor and gp130 in the different adipose tissue compartments were analyzed using RT-PCR. Circulating levels where possible, were measured in serum with ELISAs. Results We demonstrated that IL-18 and IL-6 were about 4-fold higher expressed in EAT compared to PAT (p<0.01, both) and SAT (p<0.001, both), whereas Caspase-1, IL-6R and gp130 were higher expressed in SAT compared to the other compartments (all p 0.06 - <0.001). TLR4 was significantly higher expressed in PAT compared to EAT (p=0.01) and SAT (p<0.001). No differences in the expression of IL-1β and NLRP3 were found. We could further demonstrate significant correlations between SAT and PAT expression of all the measured genes (r=0.358–0.579, all p≤0.01), except TLR4. No significant correlations between circulating levels and the genetic expression in either AT compartments were observed, and also limited correlations to BMI. Conclusions The results shows that only IL-18 and IL-6 were higher expressed in EAT, compared to the two other AT compartments in our non-obese CHD population. The results further show that the inflammasome related genes in pericardial AT associated strongly with subcutaneous AT, suggesting SAT to be more pro-inflammatory than previously expected. Funding Acknowledgement Type of funding sources: None.