Broken hearts need lymphatic vessels to heal

Lymphatic vessels support the regeneration of damaged heart tissue in zebrafish and might make a good target for therapies to promote recovery after heart attacks.

A cardiac lymphatic vessel (red) forming alongside a coronary artery in the adult zebrafish heart. Image credit: Michael Harrison (CC BY 4.0)

Human hearts have coronary vessels that supply oxygen and essential nutrients to the heart. When this supply is interrupted, a heart attack can occur. After a heart attack, scar tissue forms that impairs the heart’s ability to pump blood around the body. The heart also has lymphatic vessels that drain excess fluid and remove waste products and damaged cells from the heart. Less is known about the lymphatic vessels and their role in heart disease.

Unlike human hearts, which scar easily, the zebrafish heart can regenerate after injury. Because of this, scientists often study zebrafish to try to find ways to improve healing of heart injuries in humans. However, it is not yet known whether lymphatic vessels contribute to regeneration of zebrafish hearts.

Now, Harrison et al. show that, in the zebrafish heart, lymphatic vessels develop after the coronary arteries. In fact, the coronary arteries provide a scaffold that the lymphatic vessels grow along.

When the zebrafish are genetically modified so that they lack coronary arteries, the lymphatic vessels fail to grow. Further experiments showed that, when the heart was injured by briefly freezing part of it, extra lymphatic vessels grew, but this did not happen when a part of the heart was removed via surgery. This may be because the cold-induced injury causes inflammation, which can trigger the growth of lymphatic vessels. The lymphatic vessels then help battle inflammation, allowing regeneration to proceed. Using genetically engineered zebrafish, Harrison et al. were then able to turn the genes that control lymphatic vessel growth on and off. They showed that zebrafish lacking lymphatic vessels in the heart are less efficient at regenerating heart tissue and develop more scar tissue after injury. This result is supported by the findings of a separate study conducted by Gancz et al.

The results suggest that stimulating the growth of lymphatic vessels or enhancing their activity in the injured heart may aid recovery. More studies may help scientists understand exactly how lymphatic vessels aid regeneration in zebrafish and whether promoting lymphatic vessel growth or activity may aid heart attack recovery in humans.