Osaka, Japan – A heart attack is far from being an isolated, acute event. The consequences of an attack can cause serious and lasting damage, including heart failure. However, researchers and clinicians have been unable to determine a standardized treatment route to prevent taking long-term structural changes to the heart after a heart attack.
Now, researchers from Japan report that taking a multipronged approach to treating the damage caused by the initial attack can help reduce the chance of future serious consequences.
The team, based at The University of Osaka, has revealed that simultaneous administration of five therapeutic mRNAs can effectively reduce heart tissue damage and improve heart function in a mouse model of heart attack. The findings are set to be published in Small Science.
After a heart attack, heart failure can develop in response to several different types of damage sustained. These include inflammation, scarring of the heart tissue, the death of individual heart cells, and reduced blood flow to the heart tissue.
"The fact that a heart attack causes such complex damage to the heart makes it difficult to treat," says lead author, Kazuma Handa. "Conventional treatments that only target one of these types of damage are typically not effective."
In this study, the researchers took a multifactor approach to treating the consequences of a heart attack. Using polymer-based mRNA carriers known as a polyplex nanomicelles, they delivered mRNAs encoding five different proteins important for tissue recovery directly to the hearts of mice with heart failure.
"The results were very positive," explains Keiji Itaka, senior author. "Delivering the five-mRNA cargo to the damaged heart tissue promoted the formation of new blood vessels, inhibited scar tissue formation, increased tissue repair, and decreased the rate of heart cell death."
These effects had a profound impact on the overall health of the mice. Mice that were treated with the five mRNAs exhibited improved heart contraction, thicker heart walls, and better blood movement through the heart, all of which contributed to increased survival.
"Our findings suggest that this specific combination of five factors effectively promotes the repair of heart tissue damaged during a heart attack," notes Handa. "Taking action early, in addition to promoting repair, also ensures that heart function is not significantly impeded long-term."
This study demonstrates that treating heart tissue with multiple mRNAs involved in repairing the various signs of damage can effectively address the multifaceted nature of heart failure after heart attack. These results could serve as the foundation for a new generation of treatments for heart failure and help establish mRNA-based medicine as a new pillar of regenerative medicine.
