Secretion of adipocytokines by perivascular adipose tissue near stenotic and non-stenotic coronary artery segments in patients undergoing CABG

Abstract

Objective: Perivascular adipose tissue (pvAT) may induce a local pro-inflammatory environment, possibly contributing to coronary atherosclerosis. We investigated whether there is a difference in adipocytokine production by pvAT near stenotic and non-stenotic coronary artery segments in patients with coronary artery disease (CAD).

Methods: In patients undergoing CABG with or without valve replacement (n = 38) pvAT near stenotic and near non-stenotic coronary segments was harvested. PvAT was incubated ex vivo for 24h. Concentrations of 23 adipocytokines were measured in the supernatants with a Multiplex assay. The number of macrophages (CD68, CD11c, CD206) and lymphocytes (CD45) in pvAT was determined. Differences between stenosis and control pvAT were tested with Wilcoxon signed rank test corrected for multiple comparisons.

Results: Production of IL-5, IL-1α, IL-17, IL-18 and IL-23 was higher in control than stenosis pvAT samples (p < 0.0021). Macrophages were more abundant in stenosis than in control pvAT (median n/400× field: 2.3 IQR: 0.3-4.5 versus 1.2 IQR: 0.1-2.5). There was a predominance of M2 macrophages in both stenosis and control pvAT (median n/400× field: macrophages stenosis: M1: 0.0; M2: 1.0 p = 0.004; control: M1: 0.0; M2: 0.6 p = 0.013). The relation between adipocytokine production and macrophage infiltration was not different in stenosis and control pvAT.

Conclusion: In patients with CAD, multiple adipocytokines were secreted at higher levels by pvAT near non-stenotic than near stenotic coronary artery segments. Furthermore, pvAT macrophages are associated with stenosis of the adjacent vessel. M2 macrophages were more abundant than M1 macrophages in pvAT.

Keywords: Coronary artery disease; Cytokines; Inflammation; Macrophage polarization; Perivascular adipose tissue.