Elabela

Elabela binds the APJ receptor (APLNR) with affinity similar to apelin-13, activating Gi-coupled signaling that inhibits cAMP, activates PI3K/Akt, and triggers ERK1/2 pathways. Unlike apelin, Elabela also activates beta-arrestin recruitment to APJ more potently, which may produce distinct receptor internalization and biased signaling profiles. The downstream cardioprotective and vasodilatory outcomes of ELA and apelin APJ activation are broadly overlapping.

Elabela is highly expressed in podocytes and proximal tubular cells, where APJ signaling mediates vasodilatory effects on afferent arterioles, improving renal perfusion. In the placenta, ELA is produced by trophoblasts and regulates placental vascular development and blood flow. ELA deficiency in pregnant mice produces pre-eclampsia-like hypertension and placental insufficiency, establishing a critical developmental role beyond adult cardiovascular regulation.

Elabela infusion reduces blood pressure in hypertensive rat models through renal vasodilation, natriuresis, and suppression of the RAAS. In angiotensin II-infused hypertensive mice, ELA treatment preserved renal function and reduced proteinuria. These findings support ELA as a potential anti-hypertensive and nephroprotective agent.

Circulating Elabela levels are significantly reduced in women with pre-eclampsia compared to normotensive pregnant controls. ELA levels inversely correlate with blood pressure in pregnancy, suggesting ELA is a physiological vasodilatory hormone during gestation. ELA supplementation in a pre-eclampsia mouse model normalized blood pressure and improved fetal outcomes.

Like apelin, Elabela administration improved cardiac output and reduced fibrosis in pressure-overload heart failure models. ELA also reduced infarct size in ischemia-reperfusion models. The heart failure-relevant effects position ELA as a complementary approach to apelin-based cardiac therapies, potentially with different receptor pharmacology that could be exploited for improved efficacy.