Apelin Cardiac Fibroblast 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.Vascularization, capacity, and tone of the cardiovascular system are regulated by apelin, which counteracts the hypertensive effects of angiotensin II. This is especially true in the heart, where injury resulting in fibrosis by cardiac fibroblasts is strongly counteracted by apelin, via its induction of angiotensin II inhibitor ACE2, and via other pathways that inhibit the effects of TGF beta and SPHK1.