Researchers from the National Center for Cardiovascular Researchers (CNIC) have discovered a cellular cleaning system that is key to keeping the heart-healthy. It is a mechanism by which the contractile cells of the heart, the cardiomyocytes, release damaged components outside the cell into particles called exoferas. These exoferas are captured by a network of immune cells that live in heart tissue, macrophages, which are responsible for eliminating them before they cause inflammatory problems in the heart.
The study published in Cell collects the results of more than five years of research and collaborations with various laboratories in Europe, Asia, and the US. The information provided by this discovery suggests that cardiac dysfunction may, in some cases, stem from defects in these resident immune cells rather than cardiomyocytes, a concept with important consequences for the diagnosis and treatment of heart disease.
Until now it had been assumed that most cells were capable of disposing or recycling their waste products on their own. However, the team led by Andrés Hidalgo and José Antonio Enríquez has discovered that this process requires close collaboration between two cell types in the heart so that the material is transferred from cardiomyocytes to macrophages, which are ultimately responsible for remove waste.
‘Macrophages are cells with a high phagocytic capacity whose functions have been widely studied in the context of inflammation and disease. However, in recent years we have learned that they are also part of the majority of healthy tissues and perform important tasks in their daily function ”, explains José Ángel Nicolás Ávila, first author of the article.
The presence of these cells in the heart has been described just a decade ago and now it is beginning to be understood what exactly they do. The fact that cardiomyocytes surrogate the disposal of their waste to macrophages is a discovery that has multiple implications. Thus, Enríquez says “that the heart requires a population of macrophages to perform, among other things, cleaning tasks, suggests that many heart diseases with unknown causes may be explained by failures of these macrophages.”
Another possible implication, he notes Nicolas Avila, is the possible existence of similar processes to maintain the quality of specialized cells in other tissues, such as the brain, whose cells share characteristics similar to those of the heart. “We are currently exploring whether phenomena similar to the one we describe in the heart can occur in other organs, or if the process deteriorates with aging.”
Also, add Ana Victoria Lettuce Vieco, co-first author of the article, «cardiomyocytes are cells with a very high energy demand. The heart has to beat continuously to keep the body alive, so cardiomyocytes are filled with mitochondria, which are the organelles that produce energy. Like a cauldron, mitochondria deteriorate with use and need to be eliminated so they don’t harm the cell. The most surprising thing about our discovery -he emphasizes- is that cardiomyocytes transfer this task to macrophages, possibly because they cannot take over their cleaning tasks by themselves and, in this way, avoid the risk derived from storing damaged material in their inside”.
The number of cardiomyocytes in the heart is known to be limited and their ability to divide or regenerate in adults is greatly reduced. «That is why we believe that this phenomenon of “surrogated” elimination has evolved to allow cardiomyocytes to beat in optimal conditions for many years, while macrophages take care of their maintenance.», Indicates Hidalgo.
In summary, the work concludes, the identification of the active elimination of cardiomyocyte-derived mitochondria and other material by macrophages establishes a paradigm of how resident phagocytes contribute to the general maintenance of tissues. The idea that defects in the immune system affect health is a concept with important consequences for the diagnosis and treatment of heart disease.