EPO and heart failure: Since the HIF-PHI pathway is involved in multiple biological processes, such as the upregulation of the erythropoietin gene, promotion of tumor metastasis by stimulating epithelial-to-mesenchymal transition (Yang et al., 2008) and induction of tumor cell invasion (Meijer et al., 2012), safety concerns for HIF stabilizers including the risk of the development or progression of malignancy, diabetic retinopathy, heart failure, pulmonary hypertension, autoimmune disease, kidney fibrosis and polycystic kidney disease should be carefully concerned (Koury and Haase, 2015).