Abstract 19047: The Six-Transmembrane Protein STAMP2 Regulates Macrophage Inflammatory Responses and Protects From Atherosclerosis
The six-transmembrane protein STAMP2 plays a critical role in metabolic homeostasis and STAMP2-deficiency recapitulates most features of the metabolic syndrome in mice. As metabolic syndrome is associated with inflammation and accelerated atherosclerosis, we evaluated the role of STAMP2 in this context. We found that STAMP2 expression in macrophages was regulated strongly upon differentiation or by stimulation with inflammatory mediators. In the atherogenic ApoE−/− genetic background, STAMP2-deficiency significantly accelerated atherosclerosis both in the whole aorta and in the aortic root. This effect was independent of changes in systemic metabolism. To elucidate the mechanisms, we studied inflammatory and metabolic responses in macrophages. STAMP2-deficient primary macrophages showed an aggravated inflammatory response to lipopolysaccharide. Furthermore, STAMP2-deficiency led to increased macrophage foam cell formation and decreased cholesterol efflux of cells. Bone marrow transplantation studies showed that deficiency of STAMP2 in bone marrow-derived cells is sufficient to promote atherogenesis in ApoE−/− mice. These data suggest that STAMP2 has an important role in the control of metabolic and inflammatory responses in macrophages and a significant role in atherosclerosis.
- © 2010 by American Heart Association, Inc.