Myocardial infarction, or a heart attack, affects over 800,000 people in the United States each year. After a heart attack, a scar forms on the heart, leading to poorer heart function, and eventually it can lead to heart failure. Current treatment options are limited and have extensive side effects. Using a newly developed imaging technique, researchers at the Medical University of South Carolina, in collaboration with researchers from the University of Ottawa Heart Institute in Canada (BEaTS team, www.beatsresearch.com), revealed new insights into how injectable collagen materials have therapeutic effects potential in the treatment of heart attacks. The team of MUSC researchers was led by Peggi Angel, Ph.D.., Associate Professor in the College of Medicine. Their results were published online in Journal of the American Society for Mass Spectrometry on Oct. 29
“Before, our partner could only discover the goal of the therapy,” Angel explained, “whereas we can actually detect the therapeutic collagen peptide. We know where it has spread in the myocardial infarction. I think it’s a better way to discover the effectiveness of the treatment. on and should lead to new treatments as we will know the exact molecule attached to the site of healing. “
In this study, Angel’s team used collagen hydrogels to study how introduced collagen affects and interacts with heart attack scars. Hydrogels are large groups of molecules that consist mainly of water. The high water content makes them useful in therapy because they can carry treatments and be accepted in the body. Using a new technique, they were able to distinguish between the heart’s collagen layer and the introduced biomaterials as well as analyze their distribution throughout the heart attack wound.
Collagen is a well-known protein that is often used by diet and skin care companies. There are 28 different collagen proteins throughout the body, and each has several functions, depending on its structure and location. Angel and colleagues studied fibrillar collagen, which is different from those found in in-store products, in wound healing in the heart.
“It’s a very specific sequence compared to what can be found on the label of a commercially available collagen supplement,” Angel explained.
Using an injectable collagen material, the BEaTS team developed a therapeutic material that is localized to the heart attack area. “The biomaterial prepared by the BEaTS team stores the therapy in a specific location, such as the scar,” Angel explained. “The cells can sense the presence of biomaterials and change how they react.”
To see where the introduced therapeutic collagen ended up, Angel used MALDI-IMS, matrix-assisted laser desorption / ionization imaging mass spectrometry. Mass spectrometry is a relatively new technique that can detect charged molecules from tissue samples.
“Mass spectrometry detects ions, a molecule that has a positive or negative charge, like a small magnet. Mass spectrometry works by directing the small magnet to a detector, and we can use different ways to direct them to detect different types of molecules, said Angel.
One method of detection is IMS or imaging mass spectrometry. In MALDI-IMS, researchers can localize ions to a specific location in the tissue, in this case the heart. This allows researchers to gather spatial information about potential treatments, which is valuable for developing therapeutic agents.
In this study, laboratory mice underwent an experimental heart attack. The mice were then treated with human recombinant collagen hydrogels injected directly into the heart muscle and monitored by MALDI-IMS. To identify the injected collagens instead of the collagens made naturally in the mouse, the researchers injected human collagen. Because collagen proteins are unique to each species, the different collagens can be detected with a mass spectrometer.
The work of Angel and her team offers a new technique for studying biomaterial injections. Previous studies were only able to detect the end result of a particular treatment, but this study allows for visualization of the treatment and it is spread throughout the heart and wound area. By analyzing how treatments and therapeutic agents are distributed in a wound, researchers can evaluate the effectiveness of therapies and hopefully develop new, cleaner techniques to avoid side effects.
In the future, IMS may be used to target where therapies are most effective and determine the correct delivery site and timing. Past techniques generally required that scientists know in advance and label what they would be looking for. Mass spectrometry does not require prior knowledge or information to perform experiments and thus allows for new discoveries.
“You generally need a type of tag or known molecule to target. Mass spectrometry is easily used as a detection technique. We can detect all sorts of molecules from metabolites to lipids to proteins and even up to DNA,” Angel said.
This, combined with a greater understanding of how collagen dynamics can affect heart function, helps researchers develop new therapies that lead to a more functional heart after a heart attack. It is Angel’s goal, she said, to continue to develop innovative ways to visualize and treat illness.
Founded in 1824 in Charleston, MUSC is home to the oldest medical school in the South and the state’s only integrated academic health science center, with a unique mission to serve the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and nearly 800 residents in six colleges: Dental medicine, graduate studies, health professionals, medicine, nursing and pharmacy. MUSC raised more than $ 328 million in biomedical research funding in fiscal year 2021, and continues to lead the state in obtaining this funding. For information on academic programs, visit musc.edu.
As the clinical health care system at the Medical University of South Carolina, MUSC Health is dedicated to providing the highest quality of patient care available while training generations of competent, compassionate health care providers to serve the people of South Carolina and beyond. Close to 25,000 care team members provide care to patients in 14 hospitals with approx. 2,500 beds and 5 additional hospital sites under development, more than 300 telecommunications health centers and nearly 750 nursing homes located in the Lowcountry, Midlands, Pee Dee and Upstate regions of South Carolina. In 2021, for the seventh year in a row, US News & World Report named MUSC Health the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.
MUSC and its affiliates have collective annual budgets of $ 4.4 billion. The more than 25,000 MUSC team members include faculties, physicians, specialist providers, and world-class scientists who provide cutting-edge education, research, technology, and patient care.
Journal of the American Society for Mass Spectrometry
Evaluation of therapeutic collagen-based biomaterials in the infarcted mouse heart by extracellular matrix-targeted MALDI imaging mass spectrometry
Article Release Date
October 29, 2021