miRNA Dysregulation of AGE/RAGE Pathway in Metabolic Syndrome: A Novel Analysis Strategy Utilizing miRNA-profiling Data

Metabolic syndrome (MetS) is associated with a plethora of different comorbidities.Exploring its key molecular mechanisms, such as advanced glycation end product and its receptor (AGE/RAGE) pathway, holds great potential.Numerous sources agree that targeting the AGE/RAGE pathway is a potential therapeutic strategy for MetS.However, the regulation of AGE/ RAGE by microRNAs (miRNAs) in the context of MetS is still poorly understood.This review aimed to provide a systematic picture of the influence of miRNAs on AGE/RAGE in the context of MetS, with a particular focus on its ligands and receptors.This review achieves this in two ways: through an inductive "bottom-up" approach realized by a classical descriptive literature search, and through a deductive/synthetic "top-down" approach based on carefully selected miRNA profiling studies in MetS and its comorbidities.Although the initial inductive approach allowed the identification of some miRNAs of interest, almost all articles on this topic focus on the regulation of processes exclusively involved in atherogenesis.The new deductive approach has broadened the research horizon: It has enabled the discovery of new promising miRNAs and allowed for ranking different comorbid pathologies in MetS according to the degree of miRNA dysregulation of AGE/RAGE.Thus, in addition to atherosclerosis, significant miRNA dysregulation of AGE/RAGE was also described in MetS, particularly in immune cells, as well as in subcutaneous adipose tissue in obesity.This review, along with the novel approaches to systematizing the data contained therein may contribute to the understanding of MetS pathogenesis and the search for targets for the treatment of MetS.