This article is from WeChat official account:Academic Jingwei (ID: Global_Academia)< span class = "text-remarks">, author: WuXi PharmaTech content team, the original title: “” expected to change the treatment of heart disease! “from this small fish body, scientists have found a secret switch myocardial repair,” drawing from the title : Unsplash

At the Zhang Renqian (Victor Chang) Heart Research Institute in Sydney, Australia, there are tens of thousands of small blue and silver tropical fish-zebras The fish are swimming around in the aquarium. These little fishes are no more than 4 centimeters long, but in their slender and small bodies, they have a powerful heart beating, which is enough to make people feel uncomfortable. Scientists are exploring the secrets of Xiaoyu’s heart in order to develop new drugs to treat cardiovascular disease, the number one killer of human health.

▲Zebrafish (Picture source: Reference [2]; Credit: Victor Chang Heart Research Institute)

The adult’s heart has very poor regenerative ability. Once a heart attack (myocardial infarction), the damaged heart muscle is difficult to recover. Eventually bring various health problems.

However, scientists have discovered that zebrafish have an excellent ability to repair the heart muscle after the heart is damaged. Even after a part of the heart is removed, it can grow back in a few weeks!

How did the zebrafish heart accomplish this feat? Recently, scientists discovered the secret.

In a research paper recently published in the top academic journal Science, Zhang Renqian Heart Institute scientists for the first time confirmed a key gene for myocardial regeneration in zebrafish . This gene is like a switch that can initiate the division and proliferation of myocardial cells after a heart attack, and ultimately regenerate and completely heal the damaged myocardium. Professor Kikuchi and (Kazu Kikuch), who are in charge of this research, believe that “this discovery may completely change the treatment of heart disease. “

▲Corresponding author Professor Kikuchi and Zebrafish (Picture source: Reference [2])

The gene discovered by scientists is called Krüppel-like factor 1 (abbreviated as Klf1). In the past, people only knew It plays a role in the development of red blood cells, as a transcription factor, regulating the expression of other downstream genes. And in this new study, scientists found thatAfter zebrafish heart damage, Klf1 is specifically expressed in cardiomyocytes.

Further exploration found that activating Klf1 can return the remaining undamaged cardiomyocytes to a less mature state, and change the cell’s mitochondrial metabolism, so that these cells can divide to produce new cells. The cardiomyocytes accelerate the healing of the myocardium.

Experiments have shown that deleting the Klf1 gene of zebrafish will make their hearts lose the ability to repair themselves. This result indicates that Klf1 is essential for myocardial repair.

At the same time, this research also provides an answer to a long-controversial question in the field. Researchers have found that inhibiting the function of Klf1 in cardiomyocytes will severely impair the regenerative capacity of the heart, but will not affect the early development of the heart. “This is a clear evidence that the regeneration process after heart injury is not the same as the development process of the heart and involves completely different molecular pathways.” Professor Bob Graham of the institute commented.

Professor Graham added that using this discovery, they hope to bring revolutionary treatments to patients with heart disease. “This gene may also act as a switch in the human heart. Further research on its function will provide us with clues to turn on the regeneration of the human heart.”

Professor Kikuchi and Professor pointed out: “Considering that these small fish and humans have more than 70% of the same genes, this discovery is likely to save many lives and lead to the discovery of new drugs.”

Reference materials

[1] Masahito Ogawa et al., (2021) Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish. Science Doi: 10.1126/science.abe2762

[2] World First Discovery Uncovers Secret Switch That Could Revolutionise Heart Att