Carle Illinois-led research unlocks clues to healing damaged hearts

2/6/2023 Beth Hart

Written by Beth Hart

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How do you heal an injured heart? Research led by a Carle Illinois College of Medicine faculty member could give scientists new tools to prevent further damage and promote healing after a heart attack. The discoveries offer new insights into the inflammatory response and how it can be altered using two novel therapies.

<em>Illustration of myocardial infarction.</em>
Illustration of myocardial infarction.

Scientists have established that the inflammatory response triggered during a heart attack can cause further damage to the heart muscle and result in rhythm abnormalities if left untreated. But current treatments aimed at controlling inflammation haven’t proven very effective in preventing arrhythmias. In the new study using mice, Carle Illinois Biomedical and Translational Sciences Teaching Assistant Professor Joe Sepe and his research team from Oregon Health and Sciences University demonstrated that restoring the nerves that control the heart’s automatic functions in the days and weeks following a heart attack is key to altering the inflammatory response from a negative to a positive. “Our results show that sympathetic reinnervation of the myocardium following MI, whether through ISP or HJ-02, alters the inflammatory response to a more beneficial, reparative phenotype,” Sepe explained.

Building on earlier research by fellow researcher Professor Beth Habecker, the team demonstrated the effectiveness of two novel therapies in restoring the heart’s sympathetic (automatic) nerve functions following a heart attack. They are intracellular sigma peptide (ISP), which was originally developed to help heal nerve damage in spinal cord injuries, and a newly developed molecule called HJ-02. Sepe says more research is needed before the therapeutics could be used in humans, but the results are promising. “I think this work has enormous potential for patients who have suffered a heart attack,” Sepe said.

<em>Joseph Sepe, Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign</em>
Joseph Sepe, Carle Illinois College of Medicine, University of Illinois, Urbana-Champaign

The team also discovered that a method previously used to classify tumor tissue can help classify immune cells in the heart based on whether they are likely to be harmful or helpful. The quantitative multiplex immunohistochemistry (mIHC) method is used with hearts biopsied after the patient receives a transplant and can help scientists understand how the inflammatory process changes over time. “Having a tool such as mIHC to classify and understand the immune cell types present in the heart following a myocardial infarction (MI, or heart attack), may allow for more targeted approaches with enormous therapeutic potential,” Sepe explained.    

The team's study, "Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction," was published recently in the Journal of the American College of Cardiology.

The work is part of the emerging field of neurocardiology. Carle Illinois College of Medicine offers a neurocardiology course, taught by Professor Sepe.

Editor’s note: The work of Professors Sepe and Habecker was supported by the National Institutes of Health. The work of Dr. Lisa Coussens was supported by the NIH, the Susan G. Komen Foundation, the Knight Cancer Institute, and the Brenden-Colson Center for Pancreatic Care at OHSU. Professor Michael Cohen created and synthesized the HJ-02 molecule.

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This story was published February 6, 2023.