Micro-RNA against infarction
In the embryonic period in the heart there are rapid processes of division of cardiomyocytes – heart muscle cells – necessary for the construction of a working myocardium. Cardiomyocytes retain some proliferative ability in newborns, but lose it in adulthood. Therefore, heart diseases, including a heart attack, can have catastrophic consequences, leading to mass cell death and a decrease in myocardial function.
A number of signaling mechanisms, including the expression of micro-RNA, change during the development of the heart, negatively affecting the regenerative potential of cardiac tissue. MiR is a class of micro–RNAs expressed exclusively in the early stages of development. Their effect on the proliferation of adult cardiomyocytes and the function of the heart as a whole has not been studied.
Researchers at the Lewis Katz School of Medicine at Temple University (Temple University, Philadelphia) wondered whether miR-294 could serve as a kind of source of youth for adult cardiomyocytes: would its introduction into adult heart cells lead to an embryo-like state, allowing the creation of new cells.
The researchers tested their idea on mice with a model of myocardial infarction. For this purpose, the doxycycline-induced vector AAV9-miR-294 was delivered to mice to activate miR-294 in myocytes continuously for 14 days after myocardial infarction.
In mice treated with miR-294, the function of the left ventricle significantly improved, as well as the area of damage and apoptosis decreased eight weeks after a heart attack. Cardiomyocytes were reactivated, there were signs of re–entry into the cell cycle - the ability to produce new cells (activation of cell cycle markers and target cells miR-294 was noted eight weeks after a heart attack).
The old cardiomyocytes no longer looked like adult cells, but they were not completely embryonic either. In this intermediate state, they retained the ability to create new cells, leading to an increase in cardiac function in mice after myocardial infarction.
The researchers were able to control the expression of miR-294 by turning it on or off and thereby determining the level of proliferative activity in the heart.
The authors plan to repeat the experiment on a larger animal model. They intend to study more deeply the mechanism of action of miR-294 on heart cells: there is some evidence that it has several application points.
Article by A. Borden et al. Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Cycle Reentry After Injury is published in the journal Circulation Research.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Temple Health: Embryonic microRNA Fuels Heart Cell Regeneration, Temple Researchers Show.