Accumulation of inflammatory macrophages is a common feature in the atherosclerotic plaque and the visceral adipose tissue during obesity1, 2. In diabetes, this pathogenic process hinders the regression of atherosclerosis, and in obesity, it promotes insulin resistance and metabolic dysfunction. The ability to examine plaque and adipose tissue macrophages, and associated changes in gene expression and biochemistry within these macrophage populations during diabetes and diet-induced obesity and insulin resistance are important features of this Program Project. As such, a Core will be established to: (1) Isolate and quantify macrophage subsets, and other immune cell subsets from atherosclerotic plaque and adipose tissue by FACS, and (2) monitor changes in gene expression and metabolic parameters within atherosclerotic plaque and adipose tissue macrophages. These procedures are key to the successful execution of the Aims throughout this Program Project, and centralizing the gene expression analyses, immunohistochemical and biochemical assays will ensure consistency and reproducibility, which in turn will maximize the efficiency and productivity of the scientists within each project.
CORE B: Narrative Chronic inflammation of visceral adipose tissue is associated with obesity, and is believed to contribute to the development of systemic insulin resistance and type 2 diabetes. There is a need to better understand the mechanisms by which immune cells, particularly macrophages, accumulate in adipose tissue during high fat feeding and to identify potential signals that promote the egress of these cells from an inflamed site to promote the resolution of inflammation. This Core will centralize the biochemistry and pathology assays addressing this problem to ensure consistency and to maximize the productivity of the scientists within each project of this program.
| Koelwyn, Graeme J; Corr, Emma M; Erbay, Ebru et al. (2018) Regulation of macrophage immunometabolism in atherosclerosis. Nat Immunol 19:526-537 |
| Moore, Kathryn J; Koplev, Simon; Fisher, Edward A et al. (2018) Macrophage Trafficking, Inflammatory Resolution, and Genomics in Atherosclerosis: JACC Macrophage in CVD Series (Part 2). J Am Coll Cardiol 72:2181-2197 |
| Hadi, Tarik; Boytard, Ludovic; Silvestro, Michele et al. (2018) Macrophage-derived netrin-1 promotes abdominal aortic aneurysm formation by activating MMP3 in vascular smooth muscle cells. Nat Commun 9:5022 |
| Barrett, Tessa J; Murphy, Andrew J; Goldberg, Ira J et al. (2017) Diabetes-mediated myelopoiesis and the relationship to cardiovascular risk. Ann N Y Acad Sci 1402:31-42 |
