Abstract 17567: Infiltration and Polarisation of Macrophages in Human Adipose Tissue Control Local Adiponectin Biosynthesis in Patients With Ischaemic Heart disease
Introduction: Pro-inflammatory cytokines suppress adiponectin (AdN) expression in cultured adipocytes. However, it is unclear how systemic inflammation affects AdN biosynthesis in human adipose tissue (AT).
Hypothesis: We hypothesised that inflammation differentially affects AdN biosynthesis in distinct AT depots of patients with ischaemic heart disease (IHD).
Methods: Samples of femoral (FemAT), subcutaneous (ScAT) and thoracic (ThAT) AT collected from 258 patients undergoing coronary-artery bypass grafting (CABG), were used for gene expression and immunohistochemistry studies to determine macrophages infiltration (CD68+ cells) and M1/M2 polarization. AT from 13 additional CABG patients was incubated ex-vivo ± IL-6 (25ng/mL) and TNF-a (4ng/mL) for 24h and changes in gene expression profile and AdN release were determined.
Results: Higher circulating IL-6 was related with lower AdN (A) and PPAR-γ (not shown) gene expression in FemAT but not in ScAT or ThAT. Incubation of AT with IL-6+TNFa, also reduced AdN expression and release selectively in FemAT(B). FemAT had the highest expression of IL6-receptor (IL-6R, C) and lowest infiltration by CD68+ cells (assessed by CD68 gene expression and immunohistochemistry, D), as well as the lowest CCR7/CD206 gene expression (E) and CD40+/CD206+ cells infiltration (F) suggesting low M1/M2 macrophages ratio.
Conclusions: Infiltration of human AT with macrophages (and their M1/M2 polarisation) affects local AdN biosynthesis. AT depots with low infiltration and M1/M2 ratio, such as FemAT, are more susceptible to suppression of AdN expression by systemic inflammation. Therefore systemic inflammation is a key regulator of adiponectin levels in human atherosclerosis.
Author Disclosures: P. Coutinho: None. A.S. Antonopoulos: None. C. Psarros: None. M. Margaritis: None. J. Digby: None. M. Petrou: None. R. De Silva: None. R. Sayeed: None. K.M. Channon: None. C. Antoniades: None.
- © 2014 by American Heart Association, Inc.