ELABELA: The Heart's Hidden Helper

Discover the novel hormone revolutionizing our understanding of cardiac development and its therapeutic potential

Explore the Science

The Heart's Hidden Architect

Imagine a microscopic architect working silently during the earliest moments of life, directing the formation of that most vital organ—the human heart. For decades, scientists knew this architect existed through its effects but couldn't identify it.

Then, in 2013, researchers discovered a remarkable hormone called ELABELA (also known as Toddler or Apela), a key player in cardiac development that acts as a new endogenous ligand for the previously mysterious APJ receptor 3 .

This discovery not only solved a longstanding puzzle in developmental biology but also opened exciting new pathways for treating heart disease, hypertension, and other conditions.

Heart development visualization

The Cast of Characters

APJ Receptor

Discovered in 1993, APJ is a G protein-coupled receptor (GPCR) that resembles the angiotensin II type 1 receptor but doesn't bind to angiotensin II 5 6 .

For years, it remained an "orphan" receptor—a lock without a key—waiting for its natural ligand to be discovered.

Apelin

In 1998, researchers identified apelin as APJ's first endogenous ligand 5 6 .

This peptide was found to be widely expressed throughout the body and involved in various physiological processes, including blood pressure regulation, fluid homeostasis, and cardiovascular function 2 .

ELABELA

The search began for APJ's other activation key—a quest that would take researchers through years of investigation before finally culminating in an unexpected discovery.

The discrepancy between APJ and apelin knockout phenotypes suggested another ligand must exist 5 .

The Discovery Moment

Database Mining Breakthrough

The breakthrough came in 2013 when two independent research teams identified a previously overlooked peptide that would be named ELABELA (ELA) 3 .

The discovery was made not through traditional protein purification but by mining genetic databases for conserved sequences that might encode secreted peptides.

Zebrafish Revelations

Researchers made a crucial discovery when they found that zebrafish embryos lacking ELA developed severe heart defects or no heart at all—surprisingly mirroring the abnormalities seen in APJ-deficient embryos 3 .

This suggested that ELA and APJ were in the same biological pathway essential for proper heart formation.

The "Toddler" Connection

Simultaneously, another research group identified the same peptide and named it "Toddler" for its role in promoting cell movement during gastrulation—the stage when the embryo begins to form distinct layers 3 .

The dual naming reflects the peptide's dual functions in both early cell movement and later heart development.

Developmental Role of ELABELA

Cardiac Development Timeline

Gastrulation High ELA Expression
Heart Field Specification Moderate ELA
Heart Tube Formation Localized ELA
Chamber Formation Focused ELA

A Tale of Two Ligands: ELABELA vs. Apelin

Though both ELA and apelin activate the same APJ receptor, they exhibit fascinating differences in their expression patterns and functions 5 8 .

ELABELA

  • Chromosome 4 location
  • 54 amino acid precursor
  • Early gastrulation expression
  • Essential for heart formation
  • Kidney, prostate, endothelium distribution

Apelin

  • Chromosome X location
  • 77 amino acid precursor
  • End of gastrulation expression
  • Important for cardiovascular maturation
  • Widespread tissue distribution

Key Insight

During development, ELA expression begins earlier than apelin, explaining why APJ deficiency causes more severe defects than apelin deficiency 5 . ELA is present during gastrulation, while apelin expression only initiates later in development.

The Scientist's Toolkit

Studying a peptide hormone like ELABELA requires specialized tools and techniques. Here are some of the key reagents that have advanced our understanding of this fascinating hormone:

Function: Gene editing
Research Application: Creating specific mutations in ela genes in model organisms 3

Function: Receptor studies
Research Application: Testing ELA binding and signaling pathways 7 8

Function: Quantification
Research Application: Measuring ELA levels in blood and tissue samples 7
Gene Editing

5+

Techniques

Assay Types

8+

Detection Methods

Model Systems

4+

Organisms

Publications

200+

Research Papers

Therapeutic Horizons

The discovery of ELABELA's cardiovascular effects has ignited excitement in the medical community, particularly for treating heart disease and related conditions 4 .

Heart Failure

Heart failure remains a leading cause of mortality worldwide. The ELA-APJ system offers several potential benefits for heart failure patients:

  • Improved cardiac contractility
  • Reduced cardiac hypertrophy
  • Enhanced vasodilation
  • Increased fluid excretion 4

Animal studies show that administering ELA can improve cardiac function in models of heart failure, suggesting therapeutic potential 4 .

Preeclampsia

Pregnant women with preeclampsia show reduced ELA levels 4 .

Interestingly, ELA but not apelin knockout pregnant mice develop preeclampsia-like symptoms including proteinuria and elevated blood pressure, which can be normalized by infusion of recombinant ELA .

This suggests ELA replacement therapy might benefit preeclampsia patients.

Research Progress

Current research is focused on developing stable ELA analogs that could be used therapeutically for various cardiovascular conditions.

Preclinical Research: 30%

References