Frontier technologies for investigating endothelial heterogeneity and function in diabetic vascular disease: An...

Diabetes mellitus significantly contributes to global morbidity and mortality, primarily through its vascular complications, including both macrovascular diseases such as atherosclerosis and microvascular conditions such as retinopathy and nephropathy. Endothelial cell dysfunction, driven by chronic hyperglycemia, dyslipidemia, oxidative stress, and inflammation, is central to the pathogenesis of these complications. This review synthesizes recent advances in understanding the heterogeneity of endothelial cells across different vascular beds, highlighting how distinct molecular signatures and metabolic profiles result in varying susceptibilities and pathological outcomes in diabetic conditions. Macrovascular endothelial cells primarily respond to mechanical stimuli and are involved in atherosclerotic progression through inflammatory signaling and disturbed shear stress mechanisms. In contrast, microvascular endothelial cells exhibit tissue-specific metabolic adaptations and sensitivities, leading to barrier dysfunction, abnormal angiogenesis, and structural remodeling in conditions like diabetic retinopathy and nephropathy. Additionally, we discuss cutting-edge vascular imaging modalities, such as magnetic resonance imaging, computed tomography angiography, and optical coherence tomography angiography, which have improved the detection and characterization of diabetic vascular disease. Finally, we emphasize the transformative potential of human-derived vascularized organoids, which accurately recapitulate diabetic vascular pathology in vitro, offering promising platforms for disease modeling, drug screening, and personalized therapeutic interventions. These advanced technologies collectively enhance our ability to diagnose, understand, and treat diabetic vascular complications, paving the way toward precision medicine approaches.