Training-related changes in muscular and myocardial lymphangiogenesis: how to train the drain?

Lymphatic vascular system is a relatively rare focus of the modern cardiovascular research. In this context, the paper published by Greiwe et al. (2015)in this journal seems to represent a very important body of new evidence concerning the influence of different training regimens on lymphangiogenesis and lymphatic vessel densities in skeletal muscles and myocardium. The lymphatic system has important roles in various essential body functions, such as fluid homoeostasis, intestinal lipid absorption and immune cell trafficking (Alitalo 2011). The very basic and utmost important function of the lymphatic system is doubtlessly the fluid homeostasis, which is highly relevant for the richly perfused muscle tissue. Thus, trainingrelated increase in tissue perfusion and secretion of metabolic waste would physiologically require increased capacity of the draining system. So, muscle training should normally be accompanied by drain training. However, this obvious hypothesis has never been addressed at the molecular or microscopic level. The authors provide novel insights into lymphangiogenesis and lymphatic vessel density regulation upon chronic training and show that both skeletal and cardiac muscles definitely, but controversially adapt to chronic training regimens: chronic eccentric muscle contraction reduced lymphatic vessel density in skeletal muscles but significantly elevated the density of myocardial lymphatics. To explain this controversy, the authors suggest three mechanisms. The first mechanism is that the lymphatics are destroyed due to direct exposure of the skeletal muscles to high mechanical stress, which is different in cardiac myocardium, where the protective components of lymphatic-specific extracellular matrix seem to provide a more stable environment. The second suggested mechanism is the negative impact of training-related inflammation, which was evidently increased in skeletal muscles, but not in myocardium. And the third mechanism was suggested to be an evident transformation of initial lymphatic capillaries into larger lymphatic vessels. The discussed mechanisms might reflect the different ways of physiological adaptation of muscular and myocardial lymphatics to chronic training. And the understanding of the underlying processes is important. In particular, the fact of training-related stimulation of cardiac lymphangiogenesis and increase in the density of myocardial lymphatics might have a potential clinical relevance. As reviewed recently (Dashkevich et al. 2016), very little is currently known about the role of lymphatics in various cardiac diseases. However, the training-related modulation of lymphatic endothelial phenotype and lymphatic density might have a hypothetical impact in several cardiac pathologies. For instance, in atherosclerotic lesions, the impaired lymphangiogenesis seems to contribute to sustained inflammatory reactions in human coronary atherogenesis (Nakano et al. 2005). Furthermore, lymphatics are pivotal in the process of healing after myocardial infarction, participating in fibrosis maturation and scar formation through the drainage of excessive proteins and fluid mediated by VEGF-C