Diabetic atherosclerosis: is there a role for the hypoxia-inducible factors?

Biosci Rep. 2020 Aug 28;40(8):BSR20200026. doi: 10.1042/BSR20200026.

Abstract

Atherosclerosis is a major cause of mortality worldwide and is driven by multiple risk factors, including diabetes. Diabetes is associated with either an insulin deficiency in its juvenile form or with insulin resistance and obesity in Type 2 diabetes mellitus, and the latter is clustered with other comorbidities to define the metabolic syndrome. Diabetes and metabolic syndrome are complex pathologies and are associated with cardiovascular risk via vascular inflammation and other mechanisms. Several transcription factors are activated upon diabetes-driven endothelial dysfunction and drive the progression of atherosclerosis. In particular, the hypoxia-inducible factor (HIF) transcription factor family is a master regulator of endothelial biology and is raising interest in the field of atherosclerosis. In this review, we will present an overview of studies contributing to the understanding of diabetes-driven atherosclerosis, integrating the role of HIF in this disease with the knowledge of its functions in metabolic syndrome and diabetic scenario.

Keywords: atherosclerosis; hypoxia-inducible factors; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Atherosclerosis / diagnosis
  • Atherosclerosis / epidemiology
  • Atherosclerosis / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Blood Glucose / metabolism
  • Cell Hypoxia
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Metabolic Syndrome / diagnosis
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / metabolism*
  • Repressor Proteins / metabolism*
  • Risk Factors
  • Signal Transduction

Substances

  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • Blood Glucose
  • HIF1A protein, human
  • HIF3A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Repressor Proteins
  • endothelial PAS domain-containing protein 1