A type of immune cells called macrophages, found throughout the body’s tissues, are often referred to as the body’s clean-up crew. That is because they can switch between two modes: one that finds and destroys germs and clears the dead cells after injury and the other that helps with wound healing. How the switch is activated is not fully understood. 

Now, researchers at the Lewis Katz School of Medicine in the lab of Raj Kishore have discovered that a new type of genetic material, called circular RNAs, specifically circ-cdr1as, may play a role. Their study revealed that this circular RNA regulated macrophages—keeping them in the anti-inflammatory mode after a heart attack. 

“We are one of the very first to understand this new mechanism of how this cell switched into healing mode,” said Raj Kishore, the Vera J. Goodfriend Chair in Cardiovascular Research; professor and chair, Department of Cardiovascular Sciences; and professor in the Aging + Cardiovascular Discovery Center at Katz. 

“The study helps us better understand the role that circular RNAs play in macrophage behavior to maintain a healing state after a cardiac injury.” 

The study, “Circular RNA Cdr1as Modulates Macrophage-Mediated Cardiac Reparative Function,” was published in the October issue of Circulation Research, the official journal of the American Heart Association. All authors of the study are affiliated with the Katz School of Medicine.  

The study builds on research Kishore’s lab previously conducted, which found that a type of circular RNA acts as a sponge by soaking up harmful molecules, playing a key role in tissue repair after a heart attack.  

In this new work, the team investigated how much circ-cdr1as was present in heart cells after a heart attack. The researchers then overexpressed—or boosted—the circ-cdr1as in immune cells and injected them into the damaged part of the heart and viewed them using a fluorescent marker.   

In addition, they tested what happened when they delivered circ-cdr1as more broadly through a virus that can carry this genetic material into cells. Finally, they explored how circ-cdr1as work by turning certain related genes on and off. 

Kishore found that circ-cdr1as levels dropped in macrophages and heart muscle cells after a heart attack. When they restored circ-cdr1as in macrophages and put those cells back into the heart, the macrophages stayed in their healing, anti-inflammatory mode. This improved heart function and reduced the size of the damage.  

Kishore’s lab focuses on finding new ways to understand how heart disease develops and how the heart heals after injury. The team studies different methods to help the heart repair and regenerate itself after a heart attack, using models that closely reflect how the body works. 

Kishore also holds the titles of Laura H. Carnell Professor, professor in the Lemole Center for Integrated Lymphatics and Vascular Research and professor of medicine. 

“This study is exciting because it shows we are heading in the right direction,” said Kishore. “Ultimately, we hope that circ-cdr1as will be a promising target for therapies in the future to promote healing after cardiac injury.”