Researchers at the University of Guelph in Canada have identified a potential new drug which controls the inflammatory response in mice and offers protection against heart failure following a heart attack.
Heart attacks are one of the leading causes of death worldwide. When a heart attack occurs, the body’s inflammatory response causes a scar to form inside the heart which often leads to heart failure. Following a heart attack, patients are typically required to take medications for the rest of their lives, which can have debilitating side effects.
Following a heart attack, reperfusion of patients triggers cardiac inflammation which can cause the infarct to expand leading to heart failure. A reperfusion injury is damage to tissue caused when blood supply is returned following a period of ischemia – inadequate blood supply. In the heart, a heart attack reduces the flow of blood which prevents the heart muscle cells from getting enough oxygen. This is often caused by a blockage which partially or completely stops blood flow.
The researchers have identified a compound that can protect against reperfusion injury and prevents scarring, thus preventing heart failure. The compound has been shown to be effective if it is administered within hours of the heart attack occurring.
The compound targets a component of the circadian clock, which are genes and proteins that interact over the course of a 24-hour day and night cycle to regulate a wide range of bodily processes such as blood pressure and heart rate. The circadian clock mechanisms also play a part in the response of the body to injury, such as controlling the inflammatory response in the heart.
“Short-term targeting of the circadian driver REV-ERB with SR9009 benefits long-term cardiac repair post-myocardial ischemia reperfusion in mice,” explained the researchers. “Treatment for just one day abates the cardiac NLRP3 inflammasome, decreasing immunocyte recruitment, and thereby allowing the vulnerable infarct to heal.”
In the study, the compound was shown to reduce production of a cellular sensor called the NLRP3 inflammasome, which has been previously shown to contribute to scarring in the heart following a heart attack. When the compound was administered in conjunction with other conventional therapies, there was enhanced cardiac repair and less inflammation. That allowed healing to take place as if no heart attack had occurred.
Without scarring, there is no damage to the heart, which means the dug could prevent heart failure. We were amazed to see how quickly it worked, and how effective it was at curing heart attacks and preventing heart failure in our mouse models of the disease,” explained Tami Martino, PhD, director, Centre for Cardiovascular Investigations, University of Guelph.
The researchers are now moving onto preclinical trials to develop a new potential therapy. The researchers suggest that the compound could also be used to control adverse inflammatory responses in other parts of the body and could be used to prevent adverse inflammatory responses following valve replacement or organ transplants.
The study is detailed in the paper – SR9009 administered for one day after myocardial ischemia-reperfusion prevents heart failure in mice by targeting the cardiac inflammasome – which was recently published in the Nature Communications Biology. DOI: 10.1038/s42003-019-0595-z