In response to hypoxia, pro-PH macrophage markers arginase 1 (Arg1) and vascular endothelial growth factor-A (Vegfa) are significantly increased in bone marrow-derived (BMD) macrophages from IRS2−/− mice. A: isolated BMD macrophages from IRS2+/+ mice were stimulated with IL-4 (50 ng/mL) or hypoxia (2% O2) for 24 h. Irs2 gene expression was analyzed by quantitative RT-PCR. B: quantitative RT-PCR was used to analyze gene expression of Arg1 and Vegfa in BMD macrophages from IRS2+/+ and IRS2−/− mice. Data are expressed as means ± SD (n = 6). **P < 0.01; ****P < 0.0001; ###P < 0.001; ####P < 0.0001 versus indicated group. HYP, hypoxia; IRS2, insulin receptor substrate 2; NOR, normoxia; PH, pulmonary hypertension.