This unusual discovery could aid cardiac repair and provide new therapies to common heart diseases and hypertension
Scientists at A*STAR's Institute of Medical Biology (IMB) and Institute of Molecular and Cellular Biology (IMCB) have identified a gene encoding a hormone that could potentially be used as a therapeutic molecule to treat heart diseases. The hormone - which they have chosen to name ELABELA - is only 32 amino-acids long, making it amongst the tiniest proteins made by the human body.
The team led by Dr Bruno Reversade carried out experiments to determine ELABELA's function, since its existence was hitherto unsuspected. Using zebrafish designed to specifically lack this hormone, they uncovered that ELABELA is indispensable for heart formation. Zebrafish embryos without this gene had rudimentary or no heart at all. Their results were published in the 5 December 2013 online issue of Developmental Cell.
Deficiencies in hormones are the cause of many diseases, such as the loss of insulin or insulin resistance, that results in diabetes, and irregularities in appetite and satiety hormones that can cause obesity. Hormones are known to control functions such as sleep, appetite and fertility. However, this is the first time that scientists have revealed the existence of a conserved hormone playing such an early role during embryogenesis, effectively orchestrating the development of an entire organ.
The team also found that ELABELA uses a receptor previously believed to be specific to APELIN, a blood-pressure controlling hormone. This receptor called APJ or Apelin Receptor has dual functions - it first conveys signals from ELABELA and then from APELIN. Mutations in the Apelin Receptor also prevent the heart from forming. Zebrafish bereft of the Apelin Receptor are referred to as the Grinch, in reference to the cold and heartless cartoon character created by Dr. Seuss in 1957.
ELABELA has also been found to be expressed in human embryonic stem cells, indicating that it might have other functions beyond its role in cardiovascular development.