Interleukin-13: association with inflammation and cysteine proteolysis in varicose transformation of the vascular wall

Abstract

The present review considers current data on the structure, functions and role of interleukin-13 in the pathogenesis of vascular wall varicose transformation in terms of proteolysis and inflammatory response. It is known that interleukin-13 is able to interact with transforming growth factor-1 in diseases associated with fibrosis. The latter activates fibroblasts and excessive formation of the extracellular matrix, thereby inducing fibrosis of the vascular wall, which is one of the links in the pathogenesis of varicose veins. Also, to date, there is evidence of the interleukin-13 participation in the induction of certain proteolytic enzymes synthesis, such as matrix metalloproteinases. For the latter, participation in the transformation of the venous wall has been proven to date. The remodeling of the venous wall itself can lead to an increase in the expression of proteinases, providing a proteolytic mechanism for changing the structural organization of the venous wall in varicose veins of the lower extremities. At the same time, the involvement of lysosomal cysteine proteinases remains poorly understood. The expression and production of individual cathepsins are regulated by biologically active molecules: interleukin-1, interleukin-6, tumor necrosis factor , which are directly involved in inflammatory reactions in the wall of varicose veins. In particular, venous pathology develops in a vicious circle of inflammation with the formation of abnormal venous blood flow, chronic venous hypertension and dilation, and the recruitment of leukocytes. This leads to a further, deeper, remodeling of the walls and valves of the veins, an increase in blood pressure and the release of pro-inflammatory mediators chemokines and cytokines. In connection with the above, in order to understand the mechanisms of proteolysis in the vascular wall in varicose veins of the lower extremities, it is important to have an idea about the possible interactions of interleukin-13 with transforming growth factor-1, inflammatory cytokines, and cathepsins.