title: Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes.
abstract: The development of type-2 diabetes mellitus (T2DM) and its complications is largely due to the complex interaction between genetic factors and environmental influences, mainly dietary habits and lifestyle, which can either accelerate or slow down disease progression. Recent findings suggest the potential involvement of epigenetic mechanisms as a crucial interface between the effects of genetic predisposition and environmental factors. The common denominator of environmental factors promoting T2DM development and progression is that they trigger an inflammatory response, promoting inflammation-mediated insulin resistance and endothelial dysfunction. Proinflammatory stimuli, including hyperglycemia, oxidative stress, and other inflammatory mediators, can affect epigenetic mechanisms, altering the expression of specific genes in target cells without changes in underlying DNA sequences. DNA methylation and post-translational histone modifications (PTHMs) are the most extensively investigated epigenetic mechanisms. Over the past few years, non-coding RNA, including microRNAs (miRNAs), have also emerged as key players in gene expression modulation. MiRNAs can be actively released or shed by cells in the bloodstream and taken up in active form by receiving cells, acting as efficient systemic communication tools. The miRNAs involved in modulation of inflammatory pathways (inflammamiRs), such as miR-146a, and those highly expressed in endothelial lineages and hematopoietic progenitor cells (angiomiRs), such as miR-126, are the most extensively studied circulating miRNAs in T2DM. However, data on circulating miRNA signatures associated with specific diabetic complications are still lacking. Since immune cells and endothelial cells are primarily involved in the vascular complications of T2DM, their relative contribution to circulating miRNA signatures needs to be elucidated. An integrated approach encompassing different epigenetic mechanisms would have the potential to provide new mechanistic insights into the genesis of diabetes and its severe vascular complications and identify a panel of epigenetic markers with diagnostic/prognostic and therapeutic relevance.
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Via Tronto 10/A, 60020 Ancona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Prattichizzo
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Via Tronto 10/A, 60020 Ancona, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Giuliani
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Via Tronto 10/A, 60020 Ancona, Italy.
authors.forename: Artan
authors.initials: A
authors.lastname: Ceka
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Via Tronto 10/A, 60020 Ancona, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Rippo
authors.affiliation: Scientific Direction, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bonfigli
authors.affiliation: Experimental Models in Clinical Pathology, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Testa
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Via Tronto 10/A, 60020 Ancona, Italy ; Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Antonio Domenico
authors.initials: AD
authors.lastname: Procopio
authors.affiliation: Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Via Tronto 10/A, 60020 Ancona, Italy ; Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
keywords: Epigenetic markers of T2DM; Metabolic memory; microRNA