Pyroptosis as one of the factors of cell death and remodeling of connective tissue in type 2 diabetes mellitus

Type 2 diabetes mellitus (DM2) is a violation of carbohydrate metabolism caused by predominant insulin resistance and relative insulin deficiency or a predominant violation of insulin secretion with or without insulin resistance. The pathogenesis of DM2 is associated with systemic sluggish chronic inflammation. The pathogenesis of structural restructuring of perivascular connective tissue in DM remains the subject of close study. Matrix metalloproteinases (MMPs) are a family of extracellular proteases produced by various cell types. In the vascular wall, matrix metalloproteinases (MMPs) provide migration, proliferation, pyroptosis and apoptosis of smooth muscle, endothelial and inflammatory cells, determining intima formation and arterial remodeling. Currently, close attention is paid to a new signaling target in diabetes, where inflammation induces caspase-dependent cell death, "pyroptosis", involving Nek7-GBP5 activators to activate NLRP3 inflammasome, destabilizes the structure of parenchymal organs and neovascularization. This mechanism of cell death was called pyroptosis - "death by fire". Pyroptosis - caspase-1 is a dependent inflammatory form of cell death, which leads to the proliferation of microorganisms, host cells with increased absorption or dysfunction of affected cells. Activation of procaspase-1, which is necessary to remove uninformative sites in pre-RNA and the formation of functionally mature molecules of pro-inflammatory cytokines pro-IL-1β and pro-IL-18 occurs in contact with biochemical events with electrostatic interactions, including hydrophobic effect and proteins called inflammasomes. The study of pyroptosis of vascular wall cells and perivacular connective tissue in hyperglycemia can provide important information about the pathogenesis of DM2 and contribute to the search for new therapeutic approaches to treatment.