Beta-Adrenoceptor Activation Reduces Both Dermal Microvascular Endothelial Cell Migration via a cAMP-Dependent Mechanism and Wound Angiogenesis.
Bottom Line: Beta-adrenoceptors (β-AR) are G protein-coupled receptors (GPCRs) expressed on all skin cell-types.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
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Mentions: To investigate the effect of β-AR activation on embryonic angiogenesis, the CAM assay was performed, as described (Ausprunk et al., 1974). Representative images of CAMs 9 days post-fertilisation are presented (Fig. 7A). Iso significantly decreased angiogenesis by 45%. Similarly, an active cAMP analogue, sp cAMP, significantly decreased angiogenesis by 51% (Fig. 7B).
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK.