Abstract 4746: Adropin is a Novel and Potent Endogenous Angiogenic Neuroendocrine Peptide
Background: Therapeutic angiogenesis represents an important strategy for patients with non revascularizable coronary artery disease and ischemic cardiomyopathy. Adropin, a recently described endogenous neuroendocrine peptide, has been suggested to play a critical role in modulating normal physiological processes and maintaining metabolic homeostasis. In this study, we investigated the potential angiogenic effects of adropin.
Methods and Results: We first evaluated the time- and concentration-dependent effects of recombinant human adropin on key indices of angiogenesis in human umbilical vein endothelial cells (HUVECs). Adropin (10 ng/mL) caused a marked 10-fold increase in endothelial cell migration and proliferation and significantly increased capillary-like endothelial cell sprouting and tube formation (p<0.001). These angiogenic responses were comparable to those elicited by exogenous VEGF (100 ng/mL) and were attenuated in both adropin gene-silenced HUVECs and in HUVECs treated with monoclonal antibodies against adropin. Additionally, adropin-treated HUVECs exhibited reduced basal and inflammation-induced endothelial cell permeability indices, further suggestive of improved angiogenic potential. To identify putative adropin targets, we performed microarray expression analysis restricted to genes involved in endothelial regulation and angiogenesis. Adropin treatment markedly upregulated mRNA and protein expressions of VEGF and its receptor VEGFR2 (p<0.05) and stimulated phosphorylation of ERK1/2, a key downstream target of angiogenesis. Pharmacological inhibition of ERK1/2 phosphorylation, with the MEK inhibitor PD98059, attenuated the effects adropin had on endothelial cell migration, proliferation, tube formation and VEGF expression indicating that adropin-induced angiogenesis is ERK1/2 dependent.
Conclusions: We report, for the first time, the potent angiogenic potential of adropin, a newly described neuroendocrine peptide that is involved in metabolic homeostasis. These effects occur through stimulation of VEGFR2 expression in an ERK1/2-dependent fashion. Adropin grounded cell- and gene-based approaches may represent a novel approach in the treatment of non revascularizable ischemia.