Abstract
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.
Keywords: Endothelial progenitor cells, angiogenesis, PDE5, CXCR4, tadalafil, cGMP
Current Drug Delivery
Title: Phosphodiesterase-5 Inhibitor Tadalafil Acts on Endothelial Progenitor Cells by CXCR4 Signalling
Volume: 7 Issue: 4
Author(s): Carlo Foresta, Luca De Toni, Sabina Magagna, Alessandro Galan and Andrea Garolla
Affiliation:
Keywords: Endothelial progenitor cells, angiogenesis, PDE5, CXCR4, tadalafil, cGMP
Abstract: 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.
Export Options
About this article
Cite this article as:
Foresta Carlo, De Toni Luca, Magagna Sabina, Galan Alessandro and Garolla Andrea, Phosphodiesterase-5 Inhibitor Tadalafil Acts on Endothelial Progenitor Cells by CXCR4 Signalling, Current Drug Delivery 2010; 7 (4) . https://dx.doi.org/10.2174/156720110793360595
DOI https://dx.doi.org/10.2174/156720110793360595 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
Call for Papers in Thematic Issues
Advances of natural products, bio-actives and novel drug delivery system against emerging viral infections
Due to the increasing prevalence of viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compounds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable ...read more
Electrospun Fibers as Drug Delivery Systems
In recent years, electrospun fibers have attracted considerable attention as potential platforms for drug delivery due to their distinctive properties and adaptability. These fibers feature a notable surface area-to-volume ratio and can be intentionally designed with high porosity, facilitating an increased capacity for drug loading and rendering them suitable for ...read more
Emerging Nanotherapeutics for Mitigation of Neurodegenerative Disorders
Conditions affecting the central nervous system (CNS) present a significant hurdle due to limited access of both treatments and diagnostic tools for the brain. The blood-brain barrier (BBB) acts as a barrier, restricting the passage of molecules from the bloodstream into the brain. The most formidable challenge facing scientists is ...read more
Nanotechnology Based Chemotherapy for the treatment of Head & Neck Cancer
The escalating recurrence rates observed in Head and Neck cancer, particularly within the chemo-therapeutically treated cohort (50-60%), can be attributed to the non-selective nature of current anticancer drug delivery modalities. In this context, nanotechnology-based drug delivery systems emerge as a promising avenue for achieving precise localization of therapeutic agents to ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Miracles of Herbal Phytomedicines in Treatment of Skin Disorders: Natural Healthcare Perspective
Infectious Disorders - Drug Targets The Extracellular Matrix of Blood Vessels
Current Pharmaceutical Design Total Carotenoids Content and Assessment of Carotene Profile by High- Performance Liquid Chromatography in Selected Vegetables of Bangladesh with Special Reference to Some Unconventional Varieties
Current Chromatography Editorial (Thematic Issue: Lipid-Based Nanoformulations for Active Delivery)
Current Pharmaceutical Biotechnology Bisphosphonates: Molecular Mechanisms of Action and Effects on Bone Cells, Monocytes and Macrophages
Current Pharmaceutical Design Pharmacogenetic Applications of the Post Genomic Era
Current Pharmaceutical Biotechnology Acute Fulminant Hepatatis in Kidney Transplant Recipient After Repeated Sevoflurane Anesthesia - A Case Report and Literature Review
Current Drug Safety Overview and Findings from the Religious Orders Study
Current Alzheimer Research Linezolid - The First Oxazolidinone in the Treatment of Nosocomial MRSA Pneumonia
Recent Patents on Anti-Infective Drug Discovery A Review on CRISPR-mediated Epigenome Editing: A Future Directive for Therapeutic Management of Cancer
Current Drug Targets Correction of Murine Diabetic Hyperglycaemia With A Single Systemic Administration of An AAV2/8 Vector Containing A Novel Codon Optimized Human Insulin Gene
Current Gene Therapy Suitable Multicomponent Organic Synthesis using Heteropolycompounds as Catalysts
Mini-Reviews in Organic Chemistry Trypanocidal Activity of Nitroaromatic Prodrugs: Current Treatments and Future Perspectives
Current Topics in Medicinal Chemistry Stages of HIV Replication and Targets for Therapeutic Intervention
Current Topics in Medicinal Chemistry IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression
Current Drug Targets Protease-Activated Receptors (PARs) are Partly Pro-Inflammatory and Partly Anti-Inflammatory: Will PAR Agonists or Antagonists Participate in Future Drug Therapies?
Current Drug Targets Drug Targets for Obesity and Depression: From Serotonin to Leptin
Current Drug Targets Nutriproteomics – Linking Proteomics Variation with Personalized Nutrition
Current Pharmacogenomics and Personalized Medicine A Randomized, Double Blind, Controlled, Dose Dependent Clinical Trial to Evaluate the Efficacy of a Proanthocyanidin Standardized Whole Cranberry (Vaccinium macrocarpon) Powder on Infections of the Urinary Tract
Current Bioactive Compounds Cardiac Applications for Human Pluripotent Stem Cells
Current Pharmaceutical Design