ENDOTHELIAL DYSFUNCTION IN MUSCULAR DYSTROPHIES

Endotheliocytes are the key elements of the vascular wall and are involved in regulation of vascular tone and permeability, inflammation, hemostasis, angiogenesis etc. Impaired function of endothelial cells universally recognized as endothelial dysfunction is associated with a number of common diseases such as ischemic heart disease, arterial hypertension, atherosclerosis, peripheral arterial disease, septic shock, chronic kidney disease, obesity, oncological and autoimmune diseases. Less is known about the role of endothelial cells in pathogenesis of development and progression of rare diseases, such as muscular dystrophies. Muscular dystrophies involve over 30 genetically determined diseases, which are characterized by the development of a progressive muscular weakness and skeletal muscle degeneration. Presence of a nucleotide variant associated with a certain muscular dystrophy is primarily marked by a limited potential of skeletal muscle regeneration due to the impaired structure and function of myogenic cells. Inherited myopathies include a group of severe neuromuscular diseases caused by a mutation in the dysferlin gene DYSF, which leads to the synthesis of a dysfunctional dysferlin. Complex molecular and cellular interactions involved in skeletal muscle damage and endothelial dysfunction play an important role in the pathogenesis of dysferlinopathies. The possibility to produce an effect on different pathological aspects of dysferlin-associated myopathies such as complement system activation, inflammation, impaired function of endothelial cells, damage and necrosis of myofibrils are extensively studied in vitro and in vivo. This article is dedicated to the current understanding of relationship between the endothelium and its dysfunction in myogenesis and skeletal muscle regeneration in normal and pathological conditions caused by a group of inherited progressive myodystrophies, dysferlinopathies in particular, as well as possible clinical application of endothelial cells in treatment of muscular dystrophies.