Do Fish and Frogs Hold the Key to Heart Attack Treatment?
Researchers at Penn Medicine have been looking closely at how fish and frogs regenerate damaged heart muscle. They hope to mimic these repair mechanisms in humans. The human heart is not particularly good at repairing itself, explains Dr. Ed Morrisey, Ph.D., professor of cell and developmental biology at the Perelman School of Medicine in Philadelphia. Dr. Morrisey is the scientific director of the University of Pennsylvania’s Institute of Regenerative Medicine, where researchers are studying lower (less complex) animals. The aim is to incorporate the adaptations in these lower species to the regeneration of the human myocardium (heart muscle).
How are the hearts of lower species different from the human heart in terms of response to injury?
When a cardiac injury occurs, the heart in a lower animal is able to quickly produce cardiomyocytes (cardiac muscle cells). Research has shown that this proliferation is brought about by molecules called microRNAs, a subset of RNA that is absent in the hearts of adult mammals.
Because the circulatory system in humans and mice is a high-pressure system, an injury like an MI (myocardial infarction or heart attack) can result in rupture of the muscle and rapidly fatal loss of blood. To maintain the stability of the heart muscle following an MI, scar tissue quickly forms in the human heart. This scar tissue is life-saving in the setting of a heart attack, but is non-functional.
In lower species such as frogs and zebrafish, the circulatory system is a low-pressure one. The need for rapid scar formation to prevent blood loss is not so pressing. The hearts of these animals, therefore, can take the time to properly regenerate cardiomyocytes and form functioning cardiac muscle.
What has the research at Penn Medicine shown?
Researchers at Penn Medicine have tried inducing proliferation of cardiomyocytes in the adult mouse heart using clusters of microRNA. Increasing the expression of certain microRNA clusters was found to reactivate the proliferation of heart muscle cells. When heart attacks were induced in these mice with reactivated microRNA clusters, it was found that there was less scar formation and increased cardiomyocyte proliferation.
However, over the long term, these microRNA clusters led to decreased function in the heart muscle and the myocardium began to exhibit classic signs of heart failure. To overcome this problem, researchers used smaller molecules of the microRNA (called mimics) and injected them into the blood following a cardiac injury. This led to an increase in heart muscle proliferation for an optimum amount of time in adult mice following MI.
What do these findings mean for treatment of heart attacks in humans?
The research is still at a nascent stage, but the implications are promising and fairly straightforward. If scientists are successful in using microRNA mimics to activate cardiomyocyte proliferation in the human heart following an MI, the heart muscle will be able to repair itself following injury. The goal is to develop a system that can deliver these mimics locally to the heart at the time of injury. It will be at least another 5 to 10 years, however, before this becomes a reality.
References:
- http://www.healio.com/cardiology/practice-management/news/online/%7B4d68b6c8-fe92-44ae-b023-f58380131930%7D/institution-spotlight-cardiomyocyte-regeneration-research-a-focus-at-penn-medicine
