Diabetic endotheliopathy: RNA-binding proteins as new therapeutic targets

Int J Biochem Cell Biol. 2021 Feb:131:105907. doi: 10.1016/j.biocel.2020.105907. Epub 2020 Dec 26.

Abstract

Diabetic Endotheliopathy is widely regarded as a principal contributor to cardiovascular disease pathogenesis in individuals with Diabetes mellitus. The endothelium, the innermost lining of blood vessels, consists of an extensive monolayer of endothelial cells. Previously regarded as an interface, the endothelium is now accepted as an organ system with critical roles in vascular health; its dysfunction therefore is detrimental. Endothelial dysfunction induces blood vessel damage resulting in a restriction of blood and oxygen supply to tissues, the central pathology of cardiovascular disease. Hyperglycemic conditions have repeatedly been isolated as a pivotal inducer of endothelial cell dysfunction. Numerous studies have since proven hyperglycemic conditions to significantly alter the gene expression profile of endothelial cells, with this being largely attributable to the post-transcriptional regulation of RNA-binding proteins. In particular, the RBP Quaking-7 has recently emerged as a crucial mediator of diabetic endotheliopathy, with great potential to become a therapeutic target.

Keywords: Cardiovascular disease; Diabetes; Diabetic endotheliopathy; Hyperglycemia; Quaking; RNA-binding proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Vessels / drug effects
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Cardiotonic Agents / therapeutic use*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy*
  • Diabetic Cardiomyopathies / genetics
  • Diabetic Cardiomyopathies / metabolism
  • Diabetic Cardiomyopathies / pathology
  • Diabetic Cardiomyopathies / therapy*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Gene Expression Regulation
  • Humans
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Hyperglycemia / therapy*
  • Hypoglycemic Agents / therapeutic use*
  • Molecular Targeted Therapy / methods
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • Cardiotonic Agents
  • Hypoglycemic Agents
  • Protein Isoforms
  • QKI protein, human
  • RNA-Binding Proteins