Apelin Cardiomyocyte 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.While not essential to heart development or function, apelin regulates many aspects, inducing vasodilation, raising contractility and heart rate, and reducing reperfusion injury. Hypoxia induces apelin production by cardiomyocytes, forming a positive regulatory loop to lower stress and injury, and accommodate changes in load. These effects occur through a variety of signaling pathways, principally PKC, PLC, Ca++, and AKT. Apelin also functions in cardiac and vascular development to stimulate angiogenesis and cell migration, while reducing vascular tone, though APELA has more significant effects when deleted.