Peptide shows promise for post-heart attack healing
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When rebuilding a house after a storm, materials and design make a lot of difference. A structure may fail in the future if it was not rebuilt soundly. The same is true for our hearts.
A protein-derived molecule may aid in healing and recovery after a heart attack, according to an article published recently in the Journal of the American College of Cardiology.
The study, conducted at the University of Mississippi Medical Center, suggests that collagen matricryptins, a class of peptide, may have potential as a therapy to prevent dysfunction in the left ventricle after a heart attack.
“If you have [a heart attack], the immediate way the heart heals determines the long-term outcomes,” says Dr. Merry Lindsey, the lead author of the study, professor of physiology and medicine at UMMC, and director of the Mississippi Center for Heart Research.
After someone experiences a heart attack, also known as myocardial infarction (MI), the body responds by replacing damaged tissues with a collagen scar. Proteins play an important part in forming scar tissue and repairing the heart.
However, the process can leave the damaged parts stiff and inflexible. Lindsey said cells less affected by the heart attack will grow in size and work harder to attempt to compensate for those killed. This contributes to uneven shape and function. Over time, the heart's efficiency decreases and the ventricle can become weak and dilated. Up to one-third of heart attack patients experience later heart failure due to these complications. This makes research into preventive strategies valuable.
Lindsey said that research into the body's response to heart attacks can help physicians develop personalized treatments to prevent post-heart attack complications in the future.
Matricryptins do multiple jobs to promote healing after heart attacks. They act as a cellular distress signal, calling cells to the injured part of the heart. These cells form new blood vessels, which can help restore the heart's function. Matricryptins also prompt cells to make more proteins specifically for repair purposes.
The particular matricryptin in Lindsey's study, called C-1158/59, is a fragment derived from collagen. It gets its name from the place in the amino acid sequence -- the molecule chain that makes up proteins -- where enzymes cut the collagen to make this matricryptin available for use.
For tests in cells, mice, and humans, Lindsey and her team synthesized a version of matricryptin they could use like a drug called p1158/59. After using this product to treat injured cells, they found that cells that received the treatment healed faster and formed more advanced tube-like structures, similar to blood vessels. This was due to cells migrating faster to the injury.
Lindsey and her team treated mice with p1158/59 for a week after they had heart attacks. They discovered that those who received p1158/59 had stronger, less dilated blood vessels. They also found that the scars in their hearts contained more of a different type of collagen. This kind, known as collagen III, is more flexible and may give the heart a better shape than collagen I, from which the matricryptin was derived.
In addition, p1158/59 treatment caused 35 genes to overexpress, or produce more of, their protein products. These included proteins like collagen, for scar formation, as well as proteins that help bind cells together.
The researchers also found that human patients with higher levels of natural matricryptin in their plasma had improved cardiac function in the days following a heart attack. While C-1158/59 in human heart tissue was not directly measured, it is a promising result. Further study is need to determine if there is a long term effect on recovery.
“The data on the C-1158/59 matricryptin and the general concept of targeting the early remodeling process after MI are highly attractive,” says Dr. Wolfram Zimmermann, a professor at the University Medical Center in Göttingen, Germany, who reviewed the research in the same issue of the journal. However, he cautions that a treatment that works in mice may not necessarily work in humans.
Lindsey anticipates two future research directions. One involves basic science research in the laboratory. There needs to be better understanding of how matricryptin triggers the repair process, she said. The other is clinical research to determine the best methods to administer matricryptin as a potential treatment post-heart attack.
“It's similar to icing and heating an ankle to moderate inflammation,” Lindsey says of heart attack treatment; it decreases the chance of future injury. Someone experiencing a heart attack should seek emergency medical attention as soon as possible, she says.
The study appeared in the September 22, 2015 issue. Funding was provided by the National Institutes of Health, American Heart Association, Department of Veteran's Affairs, and the Bernard and Audre Rapoport Foundation.