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Long-Term Complications in Diabetes Mellitus and the Interrelationship of Blood Vessel Formation, Endothelial Progenitor Cells, and gDNA Methylation

  • Michael P. SarrasJr.Email author
  • Alexey A. Leontovich
Reference work entry

Abstract

Diabetes mellitus is a disease of metabolic dysregulation resulting in microvascular and macrovascular complications. As such, the endothelial cell (EC) is a fundamental cell type targeted by the hyperglycemic (HG) episodes that occur in the disease, and this causes abnormalities in the basic process of blood vessel formation (BVF). These abnormalities in BVF are seen in the acute and chronic states of DM, with the latter chronic effects termed “metabolic memory” (MM). Abnormalities in BVF in DM are based on abnormalities in the processes of vasculargenesis and subsequent angiogenesis. In humans, vasculargenesis is dependent on endothelial progenitor cells (EPCs), and these cells have been reported to be dysfunctional in DM. Studies in an animal model of DM and MM have shown that hyperglycemia induces epigenetic changes observed as gDNA hypomethylation in a loci-specific but genome-wide fashion. The role of these gDNA methylation changes as a contributing factor in the long-term complications of DM seen in MM is unclear, but may relate to dysfunctions in mechanisms involved in the regulation of gene expression. This chapter provides an overview of the interrelation of (1) DM/MM, (2) BVF, (3) EPC, and (4) gDNA methylation and proposes mechanisms to explain these relationships and experimental approaches to test the validity of these mechanisms.

Keywords

Diabetes mellitus Metabolic memory Epigenetics gDNA methylation Hypomethylation Bioinformatics Blood vessel formation Endothelial cells Endothelial progenitor cells Regulation genes of blood vessel formation 

List of Abbreviations

5mC

5-Methylcytosine

AGE

Advanced glycation end products

BVF

Blood vessel formation

CpG

Cytosine-phosphate-guanine (a dinucleotide)

CTGF

Connective tissue growth factor

CV

Cardiovascular system

DM

Diabetes mellitus

ECs

Endothelial cells

EPCs

Endothelial progenitor cells

MM

Metabolic memory

MRs

Methylated regions (of gDNA)

HUCECs

Human umbilical cord endothelial cells

HG

Hyperglycemia

ORF

Open reading frame

ROS

Reactive oxygen species

TF

Transcription factor

TSS

Transcription start site

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Cell Biology and Anatomy, Chicago Medical SchoolRosalind Franklin University of Medicine and ScienceNorth ChicagoUSA
  2. 2.Division of Biomedical Statistics and InformaticsMayo ClinicRochesterUSA

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