In this study, we obtained the first evidence that SDF-1/CXCR4 and phospho-PI3K/phospho-AKT protein expression levels are significantly greater in A2AR−/− mice than in WT mice, demonstrating that the A2AR can down-regulate the SDF-1/CXCR4-PI3K/AKT pathway in PAH. This evidence concerns the gene CXCL12 and pulmonary arterial hypertension.