Cardiovascular disease remains the world’s number one killer and advanced heart failure is a major contributor. Drawing inspiration from the plant world, WELBIO-IREC researchers have discovered how heart muscle enlargement occurs. In addition, Brahmi extract, a plant used for centuries in Indian Ayurvedic medicine, can prevent hypertrophy.
The discovery is published in the prestigious journal Science Translational Medicine.
In the process leading to heart failure, scientists have always been puzzled about how heart muscle undergoes an enlargement called hypertrophy. It has long been known that oxidative stress is a trigger of hypertrophy but exactly how oxidants trigger it is unknown, and many clinical studies have shown that anti-oxidants are ineffective.
Hydrogen peroxide: double-edged
Virginie Montiel, a cardiologist and UCLouvain professor (Institute of Experimental and Clinical Research-IREC- and Saint-Luc University Hospital) and Jean-Luc Balligand, a UCLouvain professor, WELBIO investigator and president of IREC, have managed to identify the role of hydrogen peroxide, which is also a well-known antiseptic. Produced in low concentrations by many cell types, including heart cells, it has beneficial effects. At higher concentrations, however, hydrogen peroxide sends harmful signals which, among other things, result in hypertrophy.
A solution in the plant world?
Noting that under stress cardiac cells produce hydrogen peroxide outside the cell, the researchers surveyed the plant world to understand how the compound enters the cell to activate reactions leading to hypertrophy. The cells of plant roots use proteins called aquaporins, some of which carry water and hydrogen peroxide. The researchers found that aquaporin-1 is expressed in the cardiac cells of both rodents and humans.
Several experimental approaches show that aquaporin-1 facilitates the passage of hydrogen peroxide (which makes it a ‘peroxiporin’) and regulates the development of hypertrophy in rodents and in human cardiac cells.
A promising treatment: a plant used for centuries
Looking for how to block aquaporin-1 with the help of a drug, the researchers found an answer in the plant world. The extract of Brahmi, a plant used for centuries in traditional Ayurvedic Indian medicine, contains a molecule, bacopaside, which specifically blocks aquaporin-1. And it has been shown to be effective in blocking the passage of hydrogen peroxide into cardiac cells and in preventing the development of hypertrophy.
‘Repositioning’ the remedy for cardiovascular indications
Virginie Montiel and Jean-Luc Balligand were able to confirm that a standardised Brahmi extract added to rodent food protects them against cardiac hypertrophy in response to stress such as high blood pressure. This same extract blocks aquaporin-1 in experimental models. Brahmi is easily accessible and has already been used in clinical studies for neurological diseases, without showing any notable toxicity. It could now be ‘repositioned’ for cardiovascular indications in patients at risk of developing hypertrophy that leads to heart failure. A pilot study, funded by King Baudoin Foundation, will test this hypothesis.
These encouraging results pave the way for the development of more potent molecules to block aquaporin and, the researchers hope, treat heart failure even more effectively.