Scientists find potential way to defuse ‘time bomb’ of cardiology

They have been called the ‘time bomb’ of cardiology - ascending aortic aneurysms grow for decades without any warning signs and can be fatal once they rupture. They have taken the lives of well-known actors Alan Thicke and John Ritter and are a leading cause of death in North America.

In a new study published in EBioMedicine, researchers at Western University and Lawson Health Research Institute demonstrate what might be causing these aneurysms and potentially how to treat them.

It is known that these aneurysms are caused by the thinning of the aortic wall which weakens it and makes it silently grow like a balloon over time without any symptoms. If caught early enough, they can be surgically repaired at low risk, but if they go undetected, which many do, they will eventually rupture or cause a tear in the wall of the aorta, called an aortic dissection. 

While the phenomenon is well documented, the medical community previously had little evidence to understand the mechanisms causing it to occur or how to prevent it.

Now, researchers at Lawson and Western’ s Schulich School of Medicine & Dentistry have shown that a process that is recognized in cancer biology is causing the cells to become destructive and eat away at the surrounding muscle tissue, weakening the aortic wall. 

“We discovered that within the wall of the aorta, a small proportion of the muscle cells have undergone remarkably fast aging and they have aged so much that they’ve gone into a state called senescence.  Rather than die, these senescent cells become destructive, secreting enzymes that chew the area around them,” said Dr. Geoffrey Pickering, professor at Schulich Medicine & Dentistry and Scientist at Lawson and Robarts Research Institute. 

This is important because this opens up the possibility for strategies to prevent it from occurring. Dr. Pickering points to a line of research aimed at developing therapies that flush out these inactive cells.

“There are select research groups around the world that are coming up with compounds that have shown promise in clearing out senescent cells. They are thinking about it for certain aging-related diseases, but it could be positioned for this important problem as well,” he said.

Partnering with cardiac and aortic surgeon Dr. Michael Chu, Professor at Schulich Medicine and Associate Scientist at Lawson, Dr. Pickering examined human tissue from enlarged aortas that had been surgically removed from patients before they ruptured. This group of patients have a genetic variance that causes them to have bicuspid aortic valve, and puts them at much greater risk for ascending aortic aneurysms. Bicuspid aortic valve disease is the most common congenital valve abnormality, occurring in approximately one to two percent of the general population. 

“Half of patients with bicuspid aortic valve disease will develop an ascending aortic aneurysm in their lifetime,” said Dr. Chu. “In some patients, their aneurysms grow rapidly, and in others they grow very slowly. Better understanding the mechanism contributing to ascending aortic aneurysm’s behaviour and growth will help us not only better prognosticate natural history of these aneurysms, but hopefully, lead us to new treatment options to slow or halt the growth of these aneurysms and hopefully avoid the catastrophic risks of aortic rupture or dissection.”