Apelin Endothelial Signaling Pathway

The apelin gene is X-linked and is synthesized as a 77 amino acid pre-pro-peptide that is cleaved post-translationally to generate several active forms whose lengths range from 36 to 12 amino acids. These isoforms possess similar functions but display different tissue distribution, potency and receptor binding affinity. Apelin acts as a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1), which is coupled to pertussis toxin (PTX)-sensitive G proteins. The apelin/APJ system plays important and various roles in the physiology and pathophysiology of many organs, including regulation of blood pressure, angiogenesis, cardiac contractility, metabolic balance, cell proliferation and apoptosis. It is noteworthy that the APJ receptor is also activated by APELA, a distinct peptide hormone with significant effects on cardiac development.Apelin is an angiogenic factor and mitogen of endothelial cells, participating in the normal development of the heart and blood vessels. Its expression is induced by hypoxia and shear stress. Both apelin-13 and 36 promote the assembly and proliferation of endothelial cells. The acute effect of the apelin/APJ signaling in the mature, intact endothelium is vasodilation, via activation of AKT and nitric oxide synthase, generating NO which diffuses to vascular smooth muscle cells. Promotion of vessel formation happens through multiple pathways, including AKT, ERK1/2, and JNK.