2015 : Researchers have identified a biological mechanism that enables the heart, and the body in general, to better adapt to the increasing scarcity of oxygen in the atmosphere, according to a study published on Monday. “This is the first time that we have discovered a gene responsible for adaptation to high altitude, which is essential for protecting heart function even at sea level,” said Gabriel Haddad, Professor of Pediatrics at Rady Children’s Hospital in San Diego.

This discovery could lead to the development of drugs to combat heart failure, according to researchers at the University of California School of Medicine, whose study appears in the Proceedings of the American Academy of Sciences (PNAS).

They studied the genomes of people living in the Ethiopian highlands. Like those of the Andes and Himalayas, they have undergone significant physiological and genetic changes over the millennia, affecting their respiratory and blood systems, unlike the lowland population. Sequencing of the Ethiopian genome revealed variations in the EDNRB gene apparently linked to cardiac functions and likely to explain this adaptive capacity, according to a study published in February 2014 in Genome Biology.

Researchers in California have now demonstrated this hypothesis with mice genetically engineered to reproduce this EDNRB variant, which leads to reduced production of the protein endothelin. These rodents were much more resistant to moderate or severe hypoxia, exhibiting better cardiac performance and greater oxygenation of vital organs than normal mice.

The authors’ conclusion: the lowering of endothelin levels, a powerful vasoconstrictor, resulting from this genetic variant helps preserve cardiac function in moderate to severe hypoxia. And this at high altitudes, such as sea level. Even in conditions of extreme hypoxia with only 5% oxygen – less than at the summit of Mount Everest – mice endowed with the mutant gene and therefore producing less endothelin, had significantly better cardiac and respiratory functions than other rodents.

They were able to maintain normal blood pressure and heart rate, and were better able to maintain the flow of oxygen to their vital organs.

But at this level of oxygen depletion, the respiratory capacity of normal mice dropped by 40-50%, and they were unable to maintain their blood pressure. None survived. “Lowering endothelin levels works wonders in mice placed in a low-oxygen environment, suggesting that the EDNRB gene plays a key role in human adaptation to high altitude,” noted Haddad.

According to him, this biological mechanism appears to contribute to the dilation of blood vessels and the proliferation of blood cells.

Author: Agence France-Presse, WASHINGTON