Downregulation of the C-X-C motif chemokine receptor 4 (CXCR4)/Janus kinase 2 (JAK2)/sirtuin 5 (SIRT5) signaling pathway is responsible for EPC dysfunction exacerbating HT in patients; indeed, CXCR4, which is depleted in HT samples, is able to improve SIRT5-dependent mitochondrial function via JAK2 phosphorylation [70] (Table 1). Here, JAK2 is linked to hematocrit.