Abstract 18289: Cardiac Macrophages Adopt Profibrotic/M2 Phenotype in Ischemic Hearts
Background: Macrophages (macs) that over express urokinase plasminogen activator(uPA) adapt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in ischemic mouse and human hearts and that polarization is dependent on mac derived uPA.
Methods: Mouse cardiac macs were isolated from hearts of infarcted (MI) and uninjured(UI) wild-type (WT) , uPA overexpressing (SR-uPA), or uPA null mice. RNA was extracted after isolation or culture with vehicle, IL-4 or plasmin. M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Human cardiac macs were isolated from tissue at time of LVAD placement or transplantation. Peripheral blood was collected at the same time and monocyte-derived macs (PMDM) generated. Expression of CD206 was measured in isolated and IL-4 treated macs. All values were normalized to GAPDH. Values are meanSEM
Results: Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.36.5 and 70.336, fold change vs UI, n=8, p < 0.007). ANOVA analysis of UI vs MI in WT, SR-uPA, and uPA null showed significant upregulation of Arg1 and Ym1 with MI in all genotypes (n=4-9 per genotype and condition). There was no increase in Fizz1 in any group. Treatment with IL-4 increased expression of Arg1 and YM1, to a greater degree in cardiac macs from SR-uPA versus WT mice. Human cardiac macs expressed increased levels of CD206 in comparison to PMDM (4.91.3).
Conclusions: Cardiac macs in mouse and human hearts adapt a M2 phenotype in association with cardiac fibrosis. uPA is not necessary for M2 phenotype development. Altering mac phenotype in the heart is a potential target to modify cardiac fibrosis.
- © 2013 by American Heart Association, Inc.