Elabela

The sites of APLNR receptor expression are linked to the different functions played by Elabela in the organism. Despite that, Elabela is capable of signaling independently of APLNR in human embryonic stem cells^[6] and certain cancer cell lines including OVISE.^[12]

The Elabela protein is synthesized, processed and secreted by undifferentiated human embryonic stem cells ^[7] but not mouse embryonic stem cells. In humans it is under the direct regulation of POU5F1 (a.k.a. OCT4) and NANOG.

Through autocrine and paracrine signalling, endogenous Elabela entrains the PI3K/AKT/mTOR pathway to maintain pluripotency and self-renewal.^[6]

Elabela is expressed by midline tissues (such as the notochord in zebrafish and neural tube in mammals) during organogenesis.

There it serves as a chemoattractant to angioblasts expressing APLNR at their cell surface.^[13] This participates in the formation of the first and secondary vessels of the vascular system.^[14]

The ELABELA -APLNR signaling axis is required for formation of the coronary vessels of the heart in mice through the sinus venosus progenitors.^[15]

ELA is a secreted into the bloodstream by the developing placenta. Pregnant mice lacking Ela,^[16] exhibit pre-eclampsia-like symptoms, characterized by proteinuria and gestational hypertension.^[8]

Infusion of exogenous ELA normalizes blood pressure and prevents intrauterine growth retardation in pups born to Ela knockout mothers. ELA increases the invasiveness of trophoblast-like cells, suggesting that it may enhance placental development to prevent eclampsia.^[17]

Several mimetics of ELA have been developed for therapeutic purposes. Amgen has created a camel antibody^[18] and a small molecule^[19] agonist capable of mimicking the function of ELA towards it cognate receptor APLNR.

The latter has entered phase 1 clinical trials for heart failure and acute kidney disease. Bristol Myers Squibb has also created its own small molecule agonist of APLNR.^[20]

An opinion published in the Lancet in 2019 suggested that ELABELA could be used to treat intrauterine growth restriction and maternal morbidity linked to eclampsia.^[21]