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
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Mentions: β-AR expression differs between EC type: adult human iliac vein, bovine fetal aortic (Howell et al., 1988), bovine aortic and bovine pulmonary aortic (Ahmad et al., 1990) ECs express both β1-AR and β2-AR. Retinal ECs express both β1-AR and β3-AR (Steinle, 2003), while choroidal ECs express β1-AR, β2-AR and β3-AR (Steinberg et al., 1984; Howell et al., 1988; Steinle et al., 2003; Steinle et al., 2005). However, until now, the composition of β-AR expression in primary HDMECs was not known. Western blotting studies revealed that HDMECs express the full repertoire of β-AR subtypes: β1-AR, β2-AR and β3-AR (Fig. 1).
Affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, UK.