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Handbook of Nutrition, Diet, and Epigenetics pp 849–864Cite as

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

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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.

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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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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

    Michael P. Sarras Jr.

  2. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

    Alexey A. Leontovich

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  1. Michael P. Sarras Jr.
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  2. Alexey A. Leontovich
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Correspondence to Michael P. Sarras Jr. .

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Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Sarras, M.P., Leontovich, A.A. (2019). Long-Term Complications in Diabetes Mellitus and the Interrelationship of Blood Vessel Formation, Endothelial Progenitor Cells, and gDNA Methylation. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-55530-0_71

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  • DOI: https://doi.org/10.1007/978-3-319-55530-0_71

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