Abstract 214: Role Of Sirtuin 6 In Macrophage Polarization In Diabetes
Clinical and experimental studies provide evidence that metabolic and inflammatory pathways are functionally interconnected to cardiovascular diseases. Dynamic changes in macrophage activation [classical M1 activation (promote inflammation) or alternative M2 activation (promote wound healing)], in response to various signals, modulate tissue pathology in diabetes. Sirtuin 6 (SIRT6), a NAD-dependent nuclear deacetylase plays an important role in genomic stability, cellular metabolism, stress response and aging. However, the mechanism by which SIRT6 activity affects macrophage function in diabetes is still unclear. Mouse bone marrow-derived macrophages (BMM) exposed to high glucose (HG, 25mM D-glucose) showed reduced expression of SIRT6 as compared to low glucose (LG, 5mM D-glucose)- and osmotic control (OC, 5mM D-glucose+20mM D-mannitol)-treated cells. SIRT6 knockdown in RAW 264.7 cells exaggerated inflammatory response in macrophages exposed to high glucose (HG) and in contrast, IL4-induced alternative macrophage (M2) phenotype was defective in SIRT6 deficient BM-macrophages under high glucose condition. SIRT6 protein expression was low in failing (MI-induced) and diabetes-affected hearts. Interestingly, mice receiving intramyocardial injection of SIRT6-deficient macrophages showed further deterioration in LV function, post-MI. Taken together, these data highlighting a role for SIRT6 in regulating both M1 and M2 polarization might have broad implications for numerous inflammatory disease states including insulin resistance and wound healing.
- © 2013 by American Heart Association, Inc.