Investigation of the Dysfunction Caused by High Glucose, Advanced Glycation End Products, and Interleukin-1 Beta and the Effects of Therapeutic Agents on the Microphysiological Artery Model

Adv Healthc Mater. 2024 Aug;13(21):e2302682. doi: 10.1002/adhm.202302682. Epub 2024 Apr 15.

Abstract

Diabetes mellitus (DM) has substantial global implications and contributes to vascular inflammation and the onset of atherosclerotic cardiovascular diseases. However, translating the findings from animal models to humans has inherent limitations, necessitating a novel platform. Therefore, herein, an arterial model is established using a microphysiological system. This model successfully replicates the stratified characteristics of human arteries by integrating collagen, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs). Perfusion via a peristaltic pump shows dynamic characteristics distinct from those of static culture models. High glucose, advanced glycation end products (AGEs), and interleukin-1 beta are employed to stimulate diabetic conditions, resulting in notable cellular changes and different levels of cytokines and nitric oxide. Additionally, the interactions between the disease models and oxidized low-density lipoproteins (LDL) are examined. Finally, the potential therapeutic effects of metformin, atorvastatin, and diphenyleneiodonium are investigated. Metformin and diphenyleneiodonium mitigate high-glucose- and AGE-associated pathological changes, whereas atorvastatin affects only the morphology of ECs. Altogether, the arterial model represents a pivotal advancement, offering a robust and insightful platform for investigating cardiovascular diseases and their corresponding drug development.

Keywords: advanced glycation end products (AGEs); artery; diabetes mellitus; metformin; microphysiological system.

MeSH terms

  • Arteries / drug effects
  • Arteries / metabolism
  • Arteries / pathology
  • Atorvastatin / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Glucose* / metabolism
  • Glycation End Products, Advanced* / metabolism
  • Humans
  • Interleukin-1beta* / metabolism
  • Lipoproteins, LDL / metabolism
  • Metformin / pharmacology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Onium Compounds

Substances

  • Glycation End Products, Advanced
  • Glucose
  • Interleukin-1beta
  • Metformin
  • Lipoproteins, LDL
  • Atorvastatin
  • diphenyleneiodonium
  • oxidized low density lipoprotein
  • Onium Compounds