Studying mice, researchers at Washington University School of Medicine in St. Louis have shown that boosting the activity of specific immune cells in the heart after a heart attack can protect against developing heart failure, an invariably fatal condition.
In the study, the researchers have found a way to supercharge the macrophages, increasing their abilities to digest and dispose of damaged heart tissue left in the wake of a heart attack. The key is in stimulating specialized sacs called lysosomes, which are inside immune cells. Digestion and waste disposal take place inside lysosomes.
The researchers activated a molecule called TFEB that spurred heart macrophages to make more lysosomes. In particular, TFEB also helped lysosomes digest lipids, or fat molecules, more effectively.
“Macrophages are the ‘eating cells,’ and lysosomes are like their stomachs,” said senior author and cardiologist Abhinav Diwan, an associate professor of medicine. “When we boosted the number of lysosomes, we enhanced their ability to digest damaged heart cells. Instead of provoking heart failure, this lowered inflammation and helped reduce the development of heart failure in the mice.”
In the next step, the researchers plan to investigate various small molecules as potential drug therapies that could activate TFEB and stimulate these important immune cells to improve their capacity to heal the heart following a cardiac injury, whether due to heart attack, viral infection or other forms of heart damage.
According to the Centers for Disease Control and Prevention, about 5.7 million American adults have heart failure.
The research is published on Friday in the journal JCI Insight.