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Bijnen, Mitchell; van de Gaar, Jose; Vroomen, Maria; Gijbels, Marion J.; de Winther, Menno; Schalkwijk, Casper G. and Wouters, Kristiaan (2019): Adipose tissue macrophages do not affect atherosclerosis development in mice. In: Atherosclerosis, Vol. 281: pp. 31-37

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Abstract

Background and aims: Obese individuals have a higher risk of developing atherosclerosis, possibly driven by adipose tissue (AT) inflammation. We recently showed that AT macrophages (ATMs), which accumulate in the expanding obese AT, produce mediators causing immune cell recruitment from the bone marrow. In the current study, we evaluated whether ATMs are directly involved in atherosclerotic plaque development. Methods: Lean ldlr(-/-) acceptor mice received visceral AT (vAT) from lean, obese, or ATM-depleted obese ldlr(-/-) mice. Acceptor mice were fed high cholesterol diet (HCD) for 4 weeks before and 8 weeks after AT transplantation to induce atherosclerosis. Atherosclerotic plaque development was studied 8 weeks after transplantation. Results: Transplanting donor vAT from obese mice increased circulating triglycerides and B-cells, but decreased Ly6c(-) monocytes. Plasma cholesterol, Ly6c(+) monocytes, T-cells, NK-cells and eosinophils were unaffected. Depleting ATMs from obese AT using clodronate liposomes prior to vAT transplantation prevented the increase in triglycerides and B-cells and decrease in Ly6c(-) monocytes, but did increase eosinophils. Circulating Cxcl1 was reduced by obese AT transplantation and Ifn-gamma tended to be increased while Tnf and Il-1 beta were unaffected. ATM-depleted obese AT transplantation also reduced Cxcl1, but increased circulating Tnf levels. However, obese AT transplantation with or without depletion of ATMs did not influence atherosclerotic plaque size, phenotype, or stability. Conclusions: ATMs from obese vAT do not affect atherosclerotic plaque development or phenotype.

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