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

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.,A microphysiological artery model is established by incorporating collagen, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) with perfusion via a peristaltic pump. Diabetic conditions recapitulate high glucose, AGEs, and IL-1 beta and observe physiological and morphological changes. The effects of metformin, atorvastatin, and diphenyleneiodonium are investigated to alleviate diabetic pathological changes, suggesting potential therapeutic impacts on arterial diseases. image,