Nearly a million people in the UK are living with heart failure, often a long-term consequence of damage caused by a heart attack. After a heart attack, the heart often fails to form adequate new blood vessels to fully heal. Associate Professor Sarah De Val and Dr Alice Neal have been studying the pathways regulating the formation and differentiation of vein and lymphatic vessels both in development and after a heart attack or other tissue damage. Not only are venous and lymphatic endothelial cells crucial for the correct function of the circulatory system, they can also be used as building blocks for other types of vessels.
The De Val Group’s research focuses on the study of enhancers, the on-off switches of genes, in order to identify which proteins activate the correct pattern of blood and lymphatic vessel growth during tissue repair. As part of this research, they have described multiple regulatory pathways responsible for the different aspects of blood vessels formation in the developing heart. In doing so they identified a crucial pathway that is repressed in the adult heart after injury.
“In the damaged neonatal heart, which can regenerate, we have evidence that this pathway reactivates as expected, yet the adult heart seems to be inadvertently repressing it. So, we’re trying to persuade the recalcitrant adult heart to better activate this pathway and hopefully therefore grow more of the right type of new vessels. - Professor Sarah De Val
Since it is now clear that most new vessels originate from vein endothelial cells, the De Val lab has also been very interested in how veins are formed, and how some of them know to turn into arterial cells. This is particularly important in the context of a heart attack, which is usually caused by a blockage in the left descending aorta. Some people do not have a heart attack when this region of the aorta becomes blocked because they have collateral arteries, which are direct connections between two arteries.
If we can understand how these specialised arteries are formed, and if we can get people to make them, you could not only improve blood supply after a heart attack, but potentially stop them from having heart attacks in the first place. - Professor Sarah De Val
Dr Alice Neal will be one of three researchers running as part of the BHF team, alongside patients and relatives who have benefitted from BHF research.
The BHF is our major funder. Without the BHF, a lot of this science simply wouldn't be happening. - Dr Alice Neal