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There is no doubt that research in the field of myocardial regeneration has a remarkably exciting future. This is reflected by a recent statement of the special emphasis panel at the National Heart, Lung, and Blood Institute in the USA, which was assigned to identify areas which should be in the focus of cardiovascular research within the next decades.1 It says that we need to acquire “ . . .fundamental understanding of stem cell biology, cardiogenic differentiation, and cell cycle control”. However, there are certain limitations we face when we want to embark on this field of research:
- the availability of human tissue necessary to study cardiomyocyte division is limited and the heart consists of a heterogenous cell population;
- compared to the contractile protein apparatus there is only a low abundance of most cell cycle regulating factors;
- it may be necessary to convince people that counting cells alone may not give us the right answer about tissue regeneration.
If we wish to make progress in the field of myocardial regeneration in the nearer future, there are a number of issues that need to be addressed:
which factors control cell cycle withdrawal in cardiomyocytes?
what are their upstream regulators and what are their downstream targets?
how do they interact with myogenic differentiation factors?
how do they interact with hypertrophic and/or apoptotic signals in cardiomyocytes?
Cellular division is one of the key features and the basis of life in all metazoa. Therefore, any multicellular organ has to be endowed with a programme allowing cytokinesis. However, because of specific requirements some of these cells withdraw from the cell cycle during the perinatal period and become postmitotic. This is particularly true of cells comprising central organs such as the brain and the heart. For the latter, postnatal growth—which is essential to meet the increasing demand for work to support body growth—is achieved primarily by hypertrophy. This is probably because ongoing cellular division would render the heart mechanically unstable, and thus it would not be able to establish a functional circulatory homeostasis.
In contrast to skeletal muscle cells, where differentiation and cell division …