PMID- 20695838 OWN - NLM STAT- MEDLINE DCOM- 20101116 LR - 20211203 IS - 1875-5704 (Electronic) IS - 1567-2018 (Linking) VI - 7 IP - 4 DP - 2010 Oct TI - Phosphodiesterase-5 inhibitor tadalafil acts on endothelial progenitor cells by CXCR4 signalling. PG - 274-82 AB - It has been proposed that endothelial progenitor cells (EPC), originating from the bone marrow contribute to neo-angiogenesis in vivo by forming endothelial cells. Once released in the bloodstream, EPC home at the site of vascular damage where they participate in endothelium regeneration. In this process CXCR4 plays a key role. Recently we demonstrated that a prolonged therapy with phosphodiesterase-5 (PDE5) inhibitors does improve endothelial function and increases circulating EPC, suggesting a role of PDE5 in EPC physiology. Here we tested the expression of PDE5 and CXCR4 on cultured, circulating, and bone marrow resident EPC, and we studied the effect in vivo and in vitro of PDE5 inhibition after administration of a PDE5 inhibitor (tadalafil) on EPC, in term of CXCR4 expression. We documented that in vivo and in vitro EPC express both PDE5 and CXCR4, and that tadalafil administration induced a significant increase in EPC number and the relative CXCR4 expression. This effect is inhibited by selective CXCR4 antagonist. We thus demonstrated that PDE5 inhibition acts on CXCR4 signalling in EPC and we can suppose an involvement of cGMP second messenger system in both EPC release from the bone marrow and EPC-mediated peripheral re-endothelization. FAU - Foresta, Carlo AU - Foresta C AD - Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, University of Padova, Italy. carlo.foresta@unipd.it FAU - De Toni, Luca AU - De Toni L FAU - Magagna, Sabina AU - Magagna S FAU - Galan, Alessandro AU - Galan A FAU - Garolla, Andrea AU - Garolla A LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Drug Deliv JT - Current drug delivery JID - 101208455 RN - 0 (Benzylamines) RN - 0 (Carbolines) RN - 0 (Cyclams) RN - 0 (Heterocyclic Compounds) RN - 0 (Phosphodiesterase Inhibitors) RN - 0 (Receptors, CXCR4) RN - 742SXX0ICT (Tadalafil) RN - EC 3.1.4.35 (Cyclic Nucleotide Phosphodiesterases, Type 5) RN - S915P5499N (plerixafor) SB - IM MH - Adult MH - Benzylamines MH - Carbolines/antagonists & inhibitors/*pharmacology MH - Cells, Cultured MH - Cyclams MH - Cyclic Nucleotide Phosphodiesterases, Type 5/metabolism MH - Endothelial Cells/drug effects/metabolism MH - Heterocyclic Compounds/pharmacology MH - Humans MH - Male MH - Phosphodiesterase Inhibitors/*pharmacology MH - Receptors, CXCR4/metabolism MH - Signal Transduction/*drug effects MH - Stem Cells/*drug effects/metabolism MH - Tadalafil EDAT- 2010/08/11 06:00 MHDA- 2010/11/17 06:00 CRDT- 2010/08/11 06:00 PHST- 2010/01/11 00:00 [received] PHST- 2010/05/26 00:00 [accepted] PHST- 2010/08/11 06:00 [entrez] PHST- 2010/08/11 06:00 [pubmed] PHST- 2010/11/17 06:00 [medline] AID - BSP/CDD/E-Pub/00029 [pii] AID - 10.2174/156720110793360595 [doi] PST - ppublish SO - Curr Drug Deliv. 2010 Oct;7(4):274-82. doi: 10.2174/156720110793360595.