Growth-factor treatment to mend a broken heart

A growth factor protein can promote the self-repair of heart attack damage by providing a path out of the organ for immune cells...

心脏衰竭影响半million people in the UK and occurs when the heart is unable to pump blood around the body efficiently, usually because the heart muscle has become too weak or stiff. The most common cause of this is a heart attack, which kills off a portion of the heart muscle

According to a new study published in theJournal of Clinical Investigation, scientists from the University of Oxford have now been able to identified a possible treatment to regenerate heart muscle after a heart attack and also prevent the onset of heart failure.

It was discovered a few years ago that the lymphatic vessels, which are responsible for clearing immune cells, respond to a heart attack by sprouting and growing. “We started looking at the lymphatic system in the heart a few years ago - we could never have known how pivotal it might turn out to be for heart repair,” says lead researcher Paul Riley, a British Heart Foundation Professor of Regenerative Medicine.

According to the British Heart Foundation, more than a quarter of deaths in the UK are caused by heart disease. During a heart attack, the heart is starved of oxygen and the heart muscle is damaged. Our body’s natural response after a heart attack is to send immune cells to the heart to help get rid of the dying or dead heart muscle cells. Although the immune cells do help the heart to heal, too many are released to try and repair the damage. This leads to inflammation which is like a double-edged sword, a small amount of immune cells aren’t enough to clear the damaged muscle cells but too many can cause damage in its own right.

The treatment Riley’s team worked on involves using a protein called VEGF-C, or Vascular Endothelial Growth Factor C, to help promote growth of a network of lymphatic vessels. This allowed the vessels to quickly dispose of immune cells after helping to repair and clear dying and dead heart muscle cells.

To test the process, mice that had sustained heart attacks were injected with VEGF-C. Animals treated in this way showed a significant reduction in the amount of damage to the heart muscle when compared to mice that were not treated with VEGF-C. In these animals, the heart also recovered almost all of its pumping function.

So how do we know how many of the immune cells to dispose of?

“我认为关于不同类型的cells that we are clearing is something we still need to investigate properly. Understanding which cells have we cleared, trafficked out to these lymph nodes, versus those that are left behind in the heart, and the balance of good versus bad immune cells. So there’s still work to be done in that area,” says Riley.

Whilst the treatment is not currently being investigated in humans, Riley and his team were able to set up human cell based models in a dish to form pseudo vessels. The pseudo vessels can then be tested across various medical conditions. The next step is to take this knowledge to develop drugs to promote the sprouting and growth of lymphatic vessels within the next 5 to 10 years.

“We now know that it’s not enough to just get healing immune cells into the heart,” continues Riley. “We need to boost the routes that remove these immune cells once they’ve done their job, so that they don’t start causing more harm and ultimately contribute to the long-term damage that leads to heart failure.”