Activation analysis; Biomedical engineering; Blood vessels; Diseases; Failure (mechanical); Medical problems; Oxidative stress; Proteins; Advanced glycation end products; Cytokines; Hexosamine pathway; Hexosamines; Inflammation; Nephropathy; Polyol pathway; Reductive stress; Retinopathy; Vascular complications; Chemical activation; Pathology
Diabetes is characterized by hyperglycemia, chronic oxidative stress, and inflammation; all of them contribute to the development of microvascular (neuropathy, retinopathy, and nephropathy) and macrovascular complications of this disease. Episodes of postprandial and persistent hyperglycemia drive several mechanisms leading to vascular complications, including increased reductive/oxidative stress, activation of polyols and hexosamine pathways, protein kinase C activation, and formation of advanced glycation end products (AGEs). As a consequence, chemical alterations of macromolecules alter their functions, some toxic metabolites are accumulated (methylglyoxal, sorbitol), and pro-inflammatory (TNFa, IL-1ß, IL-6, cyclooxygenase 2, MCP-1), pro-fibrotic (TGFß, collagen), and prothrombotic (PAI-1) proteins are upregulated. These changes lead to endothelial dysfunction and tissue damage inflammation, fibrosis, and altered vascularization, which finally are associated with severe health problems (neuropathic pain, loss of extremities, retinal vascularization and blindness, glomerulosclerosis and renal failure, atherosclerosis, cardiomyopathy, and heart failure). Targeting some of these mechanisms may provide new strategies for prevention and treatment of vascular complications. © Springer Nature Switzerland AG 2019