Recently, adipose tissue macrophages (ATMs) have been widely studied because of their association with an increase in fat mass and their involvement in the genesis of insulin resistance. However, little is known about the phenotype and functions of human ATMs. In this regard, this study investigated human subcutaneous adipose tissue to characterize the phenotype of the human ATMs, define their contribution to the production of adipokines and analyze their potential changes based on the degree of adiposity as well as their function within the adipose tissue mass. Results of this study showed that ATMs from lean to overweight individuals co-expressed several pro-inflammatory [tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), IL-23, monocyte chemoattractant protein-1 (MCP-1), IL-8, cyclooxygenase-2 (COX-2)] and anti-inflammatory [IL-10, transforming growth factor-beta (TGF-β), alternative macrophage activation-associated cc chemokine-1 (AMAC-1), cyclooxygenase-1 (COX-1)] factors. Furthermore, ATMs specifically produced and released the key matrix remodelling enzyme matrix metalloproteinase-9 (MMP-9) compared to mature adipocytes and capillary endothelial cells. Interestingly, this secretion of MMP-9 from human adipose tissue in vivo, assessed by arteriovenous difference measurement, appeared to be correlated with body mass index. Finally, ATMs exerted a marked proangiogenic effect on adipose tissue-derived endothelial and progenitor cells. These findings suggest that ATMs may be active players not only in adipose tissue development via their proangiogenic effects, but also in the genesis of obesity-associated cardiovascular pathologies through their production of the proatherogenic MMP-9.
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