Figure 5.

The Ca²⁺ toolkit in endothelial colony forming cells (ECFC). Growth factors, such as VEGF, and chemokines, such as stromal derived factor-1α (SDF-1α), bind to specific RTK and G_q/11PCR, thereby activating multiple PLC isoforms, which in turn cleave PIP₂ into InsP₃ and DAG. InsP₃ triggers ER-dependent Ca²⁺ release through InsP₃R, while DAG gates TRPC3 exclusively in umbilical cord blood-derived ECFCs. SOCE is the major Ca²⁺ entry pathway also in ECFC, in which it is mediated by the dynamic interplay among STIM1, Orai1 and TRPC1. Endogenous Ca²⁺ release is further supported by NAADP, which evokes EL Ca²⁺ release through TPC1. SERCA and PMCA contribute to maintain resting Ca²⁺ levels and clear cytosolic Ca²⁺ after a pro-angiogenic Ca²⁺ signal. Pro-angiogenic Ca²⁺ signals may also be delivered by TRP Vanilloid 1 (TRPV1) and TRPV4. See Section 5.2. (SDF-1α) and Section 5.3. (VEGF and NAADP) for further details.