Molecular factors involved in the development of diabetic foot syndrome.

Abstract

Diabetes is one of the major challenges of modern medicine, as it is considered a global epidemic of the XXI century. The disease often leads to the development of serious, health threatening complications. Diabetic foot syndrome is a characteristic set of anatomical and molecular changes. At the macroscopic level, major symptoms are neuropathy, ischemia and chronic ulceration of the lower limb. In every third patient, the neuropathy develops into Charcot neuroarthropathy characterized by bone and joints deformation. Interestingly, all these complications are a result of impaired healing processes and are characteristic for diabetes. The specificity of these symptoms comes from impaired molecular mechanisms observed in type 1 and type 2 diabetes. Decreased wound and fracture healing reflect gene expression, cellular response, cell functioning and general metabolism. Here we present a comprehensive literature update on the molecular factors contributing to diabetic foot syndrome.

Oxidative Stress and MicroRNAs in Vascular Diseases

“…Moreover, diabetic cardiomyopathy is a major diabetic complication; diabetes and impaired glucose tolerance increase cardiovascular disease risk 3- to 8-fold [111]. Finally, new blood vessel growth in response to ischemia is impaired in diabetes, resulting in decreased collateral vessel formation in ischemic hearts and in non-healing foot ulcers [112]. …”

Syndecan‐4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes

“…[11] To examine whether syndecan-4 proteoliposomes could significantly overcome growth factor resistance in an animal model, we placed ob/ob mice on high fat diet for 10 weeks to create a severe diseased state (Figure. 2A).…”

Genetic and molecular basis of diabetic foot ulcers: Clinical review

“…Metabolic memory has been verified at a level of genome-wide DNA methylation (38,39) in the form of defined histone modifications (36,38,40), microRNA expression patterns (41,42) and specific modulation of epigenetic regulatory machinery in diabetes related tissues such as neural and vascular cells in animal and human studies (34,41). This kind of epigenetic mechanism might contribute to the overall picture of DFU by changing expression of genes required for proper wound healing (42,43). These methods permit cells to quickly respond to altered environmental provocations (44,45) as well as allowing cells to "memorise" these events upon the removal of stimuli (46,47).…”