Billions of cardiac muscle cells are lost during a heart attack. The human heart cannot replenish these lost cells, so the default mechanism of repair is to form a cardiac scar.
While this scar works well initially to avoid ventricular rupture, the scar is permanent, so it will eventually lead to heart failure and the heart will not be able to pump as efficiently as before the damage caused by heart attack.
Zebrafish, a freshwater fish native to South Asia, is known to be able to fully regenerate its heart after damage due to the formation of a temporary scar as new cardiac muscle cells are formed.
Professor Paul Riley and his team at the University of Oxford have been striving to understand and compare the composition of the cardiac scar in different animals as part of ongoing efforts to investigate whether it can be modulated to become a more transient scar like that of the zebrafish, and therefore potentially avoid heart failure in heart attack patients.
To do so, the researchers used three different models of studying heart repair and regeneration; the adult mouse heart, which behaves in a similar way to the human heart, the neonate mouse heart, which can regenerate up to 7 days after being born before losing that ability as the mouse ages, and the zebrafish which can regenerate the heart up to adulthood through forming a transient scar.
Professor Paul Riley said:
Efforts to treat heart attack with cell replacement strategies to-date have largely failed with disappointing clinical trial results. One reason for this is the local environment into which the new cells emerge: a cytotoxic mixture of inflammation and fibrosis which prevents their engraftment and integration with survived heart tissue.
Consequently there is an urgent unmet clinical need to condition the local injury environment for efficient replacement of lost tissue. Major targets for this are the immune cells which invade the heart after injury causing inflammation, and the process of scar formation itself (fibrosis) during which immune cells signal to myofibroblasts to deposit collagen."
The team focused their efforts on studying the behaviour of macrophages, cells normally associated with inflammation and fighting infection in the body, when exposed to the three post-injury environments. They extracted macrophages from each model to examine their gene expression.
In both mouse and fish macrophages, they found that they were showing signs of being directly involved in the creation of the molecules that form part of the cardiac scar, and particularly collagen, which is the main protein involved. Related Stories
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