title: Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications.
abstract: The vascular complications of diabetes significantly impact the quality of life and mortality in diabetic patients. Extensive evidence from various human clinical trials has clearly established that a period of poor glycemic control early in the disease process carries negative consequences, such as an increase in the development and progression of vascular complications that becomes evident many years later. Importantly, intensive glycemic control established later in the disease process cannot reverse or slow down the onset or progression of diabetic vasculopathy. This has been named the glycemic memory phenomenon. Scientists have successfully modelled glycemic memory using various in vitro and in vivo systems. This review emphasizes that oxidative stress and accumulation of advanced glycation end products are key factors driving glycemic memory in endothelial cells. Furthermore, various epigenetic marks have been proposed to closely associate with vascular glycemic memory. In addition, we comment on the importance of endothelial progenitors and their role as endogenous vasoreparative cells that are negatively impacted by the diabetic milieu and may constitute a "carrier" of glycemic memory. Considering the potential of endothelial progenitor-based cytotherapies, future studies on their glycemic memory are warranted to develop epigenetics-based therapeutics targeting diabetic vascular complications.
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast BT12 6BA, UK.
authors.forename: Poojitha
authors.initials: P
authors.lastname: Rajasekar
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast BT12 6BA, UK.
authors.forename: Christina L
authors.initials: CL
authors.lastname: O'Neill
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast BT12 6BA, UK.
authors.forename: Lydia
authors.initials: L
authors.lastname: Eeles
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast BT12 6BA, UK.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Stitt
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, Belfast BT12 6BA, UK.
authors.forename: Reinhold J
authors.initials: RJ
authors.lastname: Medina
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019175:DNA Methylation; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D066026:Endothelial Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D044127:Epigenesis, Genetic; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress; D055153:Stem Cell Niche
chemical_list: D017127:Glycation End Products, Advanced; D035683:MicroRNAs