Ottawa, ON – Researchers from the Ottawa Heart Institute have found a new heart failure-protective protein. In findings published this month in Nature Communications, the researchers detail the protective role of a new protein called HACE1. They had found it to be present at increased levels in the blood of patients with heart failure, prompting them to look further at its function in the heart. This research is made possible thanks to funding from the Canadian Institutes of Health Research (CIHR).
Protecting the heart from injury so that it does not fail is the “holy grail” to prevent heart failure, said Peter Liu, MD, scientific director of the University of Ottawa Heart Institute. Very few new approaches have emerged recently to ameliorate heart failure, but now Dr. Liu and his colleagues have uncovered an exciting new possibility, that also has broader implications for other chronic diseases.
What makes these findings particularly interesting is that Dr. Liu and his colleagues had previously found that HACE1 is important in protecting against tumour growth and metastasis in many forms of cancer (published in Nature Medicine, 2007). This previous link to multiple cancers suggests that HACE1 may be an important player in cleaning up damage caused by many forms of chronic diseases.
Using human cells and mouse models, the investigators found that HACE1 is critical in regulating the removal of damaged proteins from cardiac cells after injury. Without this housekeeping function, heart tissue rapidly accumulates damaged proteins which, in time, interfere with normal function.
“People with high blood pressure, diabetes or chronic valve leakage can have heart failure, too. So why, when the muscle is intact, is the heart failing and not working properly? The likelihood is that when stress is placed on the heart, the proteins get damaged and accumulate. And if you don’t have a mechanism to turn over these proteins and get good proteins back, the heart gradually lose its sophisticated coordination and function,” said Dr. Liu.
When having a stressor that causes damage to the proteins, which accumulate in cells and make the situation worse, the damaged proteins trigger the appearance of HACE1 to remove the offending proteins to improve cell function. HACE1 appears to be one of a new class of protein quality control “police” that only appears in times of cellular stress.
The researchers are now looking for ways to facilitate or enhance HACE1 action and searching for other proteins that may play a similar role. “The intriguing possibility is that, if you could augment this system, you could help to protect the heart from failing as we age,” said Dr. Liu. “And it could help to ameliorate other chronic diseases, too.”
Heart failure is a weakness in the pumping function of the heart muscle, leading to shortness of breath and fluid buildup in the patient, and visits to the emergency room. One in 5 North Americans will succumb to heart failure, and it is one of the most costly and deadly chronic conditions. Heart failure is usually the result of damage to the heart muscle caused by a heart attack, high blood pressure, diabetes, or a virus.