Circulation: Cell reprogramming may reverse the body's heart fibrosis caused by a heart attack

Because adult cardiomyocytes have little ability to regenerate, resident cardiac fibroblasts synthesize extracellular mechanisms and form fibrosis after myocardial infarction (MI), leading to cardiac dysfunction and heart failure
。 Recently, a research report entitled "Direct Reprogramming Improves Cardiac Function and Reverses Fibrosis in Chronic Myocardial Infarction" published in the international journal Circulation, scientists from Keio University School of Medicine and other institutions in Japan discovered a new method.
It may help repair heart damage
in people who have suffered chronic heart attacks and heart failure.

In the article, the researchers suggest that changing the programming of heart cells by adjusting the expression of several key genes may actually reverse the lasting damage
caused by a heart attack.
Adult heart cells have a very limited ability to form new heart tissue, so when a heart attack damages the heart muscle, the damaged area is filled with inelastic scar tissue, the presence of which can impair heart function and lead to arrhythmias, progressive heart failure, and eventually the
death of the patient.

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Researcher Masaki Ieda said previous findings have shown that reprogramming cardiac fibroblasts (the type of cells that produce scar tissue) into cardiomyocytes (CMs) or normal heart muscle cells can improve heart function in patients with acute myocardial infarction; However, it is unclear whether reprogramming of the heart restores the function
of a damaged heart that carries an established scar.
To explore this possibility, the researchers developed a mouse model in which a therapy called tamoxifen activates overexpression of cardiac transcription factors, including a gene called Mef2c/Gata4/Tbx5/Hand2 (MGTH) to program cardiac fibroblasts into CMs, which the researchers then induced heart attacks in mice, using them to subdivide a month later to treat the mice to activate changes in cell types and determine their effects on the heart
。

The results showed that in these mice, cardiac reprogramming could convert about 2% of cardiac fibroblasts into CMs, which significantly improved the body's cardiac contractility and reduced the occurrence of fibrosis; Detailed genetic analysis results showed that overexpression of MGTH may activate the reconstruction of heart muscle and inhibit the formation of scar tissue and inflammation; Importantly, this method not only prevents the formation of additional scar tissue, but also reverses the formation
of already established scar tissue.
The results suggest that cardiac reprogramming may be able to repair the persistent damage
caused by heart attacks by regenerating the heart muscle and reducing harmful fibrosis.

Given the few effective clinical therapies currently available for patients experiencing heart attacks, this direct cardiac reprogramming approach may be promising as a potential new therapy that can not only help improve heart function in these patients by regenerating heart tissue and reversing scarring, but also reduce the risk of death due to heart failure; These findings may open up a potential avenue of research to enable this treatment
for patients.
In summary, the results of this study suggest that cardiac reprogramming may help repair chronic myocardial infarction through myocardial regeneration and the decline of fibrosis levels, which may provide new clues and ideas
for later scientists to develop new therapies for chronic myocardial infarction and heart failure.
(Biovalley Bioon.
com)

Original source:

Hidenori Tani,Taketaro Sadahiro,Yu Yamada, et al.
Direct Reprogramming Improves Cardiac Function and Reverses Fibrosis in Chronic Myocardial Infarction, Circulation (2022).
DOI: 10.
1161/CIRCULATIONAHA.
121.
058655