Beta-Adrenoceptor Activation Reduces Both Dermal Microvascular Endothelial Cell Migration via a cAMP-Dependent Mechanism and Wound Angiogenesis.
Bottom Line: They play a role in wound repair but their specific role in angiogenesis is unknown.In this study, a range of in vitro assays (single cell migration, scratch wound healing, ELISAs for angiogenic growth factors and tubule formation) were performed with human dermal microvascular endothelial cells (HDMEC) to investigate and dissect mechanisms underpinning β-AR-mediated modulation of angiogenesis in chick chorioallantoic membranes (CAM) and murine excisional skin wounds. β-AR activation reduced HDMEC migration via cyclic adenosine monophosphate (cAMP)-dependent and protein kinase A (PKA)-independent mechanisms as demonstrated through use of an EPAC agonist that auto-inhibited the cAMP-mediated β-AR transduced reduction in HDMEC motility; a PKA inhibitor was, conversely, ineffective.In more complex environments, β-AR activation delayed HDMEC tubule formation and decreased angiogenesis both in the CAM assay and in murine excisional skin wounds in vivo. β-AR activation reduced HDMEC function in vitro and angiogenesis in vivo; therefore, β-AR agonists could be promising anti-angiogenic modulators in skin.
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK.Show MeSH
Related in: MedlinePlus
Mentions: To evaluate if β-AR activation altered skin wound angiogenesis, excisional murine skin wounds were treated daily with gel alone or containing 0.1% salbutamol (approximately 1.7 mM) which, at this concentration, similar to Iso, can activate all β-ARs (Baker, 2010). Salbutamol was chosen for the in vivo study as it is already widely used to treat asthma (Boskabady and Saadatinejad, 2003), therefore, should a potential clinical application be discovered, translation to the clinic could be fairly rapid through a repurposing of medicine route. Sections of murine wounds excised after 5 days were immunostained with an antibody to CD31. β-AR activation significantly reduced the number of blood vessels by an average of 56% (Fig. 8).
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK.