Loss of either HIF-1⍺ or HIF-2⍺ does not result in a compensatory increase in the other isoform in macrophages. (A) Flow cytometric analysis of lysozyme M expression in heart (cardiomyocytes [CM], fibroblasts, and macrophages) and peripheral blood (neutrophils, Ly6C^hi monocytes) using LysM-eGFP mice, which express EGFP under the control of the LysM promoter region. C57BL/6J mice served as a negative staining control. n = 1/group from a single experiment. (B) Percent infarct/LV, percent AAR/LV, and percent infarct/AAR measured 7 d after MI in C57BL/6J, LysM-Cre⁺, Hif1^fl/fl, or Hif2^fl/fl mice. n = 5–11 mice/group pooled from more than three independent experiments. ns, one-way ANOVA followed by Tukey’s test. (C and D) Expression of HIF-1⍺ (C) or HIF-2⍺ (D) in cardiac macrophages from mice with myeloid-specific deletion of Hif1 (mHIF1^−/−) or Hif2 (mHIF2^−/−) compared with controls 5 d after MI. n = 5 mice/group pooled from two independent experiments. ***, P < 0.001 by one-way ANOVA followed by Tukey’s test. (E and F) Expression of HIF-1⍺ (E) or HIF-2⍺ (F) in BMDMs from mice with myeloid-specific deletion (mHIF1^−/−, mHIF2^−/−, and mHIF1/2^−/−) or overexpression (mHIF1^LSL and mHIF2^LSL) of HIFs cultured under normoxia (21% O₂) or hypoxia (1% O₂) for 3 h. n = 4 sets of cells/group. Data are representative of two independent experiments. ***, P < 0.001 by one-way ANOVA followed by Tukey’s test. All data presented as mean ± SEM.