The NLRP3 inflammasome activation in subcutaneous, epicardial and pericardial adipose tissue in patients with coronary heart disease undergoing coronary by-pass surgery

Sissel Åkra; Ingebjørg Seljeflot; Bjørn Braathen; Vibeke Bratseth; Charlotte Holst Hansen; Harald Arnesen; Theis Tønnessen; Svein Solheim

doi:10.1016/j.athplu.2022.03.005

The NLRP3 inflammasome activation in subcutaneous, epicardial and pericardial adipose tissue in patients with coronary heart disease undergoing coronary by-pass surgery

Atheroscler Plus. 2022 Mar 24:48:47-54. doi: 10.1016/j.athplu.2022.03.005. eCollection 2022 Apr.

Authors

Sissel Åkra¹, Ingebjørg Seljeflot^{1

2}, Bjørn Braathen³, Vibeke Bratseth¹, Charlotte Holst Hansen¹, Harald Arnesen^{1

2}, Theis Tønnessen^{2

3}, Svein Solheim¹

Affiliations

¹ Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.
² Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway.

Abstract

Background and aims: Epicardial and pericardial adipose tissue (EAT and PAT) associate with atherosclerosis, however, discussed to have different inflammatory properties. We examined the NLRP3 inflammasome related pathway, playing a pivotal role in atherosclerosis, in EAT, PAT and subcutaneous AT (SAT), their relationship to cell types and anthropometric measures in patients undergoing coronary artery bypass grafting.

Methods: Biopsies from EAT, PAT and SAT were collected from 52 patients with coronary heart disease (CHD) (median body weight 85.0 kg) and 22 controls. RNA was extracted and expression of interleukin (IL)-1β, IL-18, NLRP3, Caspase-1, toll-like receptor 4 (TLR4), IL-6, IL-6 receptor and gp130 were analyzed by RT-PCR.

Results: Limited differences in any genes between CHD patients and controls. IL-18 and IL-6 were 4-fold higher expressed in EAT versus 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). Significant correlations between SAT and PAT gene expressions (r = 0.358-0.579, all p ≤ 0.01). Especially NLRP3 and TLR4 associated with the expression of macrophages in all compartments (all p < 0.001). In EAT IL-18 correlated inversely with the expression of macrophages and T-cells. In SAT and PAT most of the mediators associated with body weight.

Conclusions: Higher expression of IL-18 and IL-6 was observed in EAT in our non-obese CHD patients, not related to inflammatory cells. The NLRP3 inflammasome activation in SAT that mirrored PAT, both related to anthropometrics, suggest that SAT samples, being easily available, to a certain degree, represent adipose tissue inflammation in general.

Keywords: Coronary heart disease; Epicardial adipose tissue; Interleukin-18; Interleukin-6; NLRP3 inflammasome; Pericardial adipose tissue; Subcutaneous adipose tissue.