Ceramides in peripheral arterial plaque lead to endothelial cell dysfunction

作者：Rodrigo Meade, Yang Chao, Nikolai Harroun, Chenglong Li, Shahab Hafezi, Fong‐Fu Hsu, Clay F. Semenkovich, Mohamed A. Zayed · 发表于：JVS Vascular Science · 年份：2023 · DOI：10.1016/j.jvssci.2023.100181 · 被引用次数：11 · 研究领域：Sphingolipid Metabolism and Signaling、Caveolin-1 and cellular processes、Diabetic Foot Ulcer Assessment and Management

Background: Peripheral arterial atheroprogression is increasingly prevalent, and is a risk factor for major limb amputations in individuals with risk factors such as diabetes. We previously demonstrated that bioactive lipids are significantly altered in arterial tissue of individuals with diabetes and advanced peripheral arterial disease. Methods: Here we evaluated whether sphingolipid ceramide 18:1/16:0 (C16) is a cellular regulator in endothelial cells and peripheral tibial arterial tissue in individuals with diabetes. Results: < .005) following exogenous supplementation with C16. Conclusions: Our findings suggest that C16 is a tissue biomarker for peripheral arterial disease severity in the setting of diabetes, and can impact endothelial cell viability and function. Clinical relevance: Peripheral arterial disease and its end-stage manifestation known as chronic limb-threatening ischemia (CLTI) represent ongoing prevalent and intricate medical challenges. Individuals with diabetes have a heightened risk of developing CLTI and experiencing its complications, including wounds, ulcers, and major amputations. In the present study, we conducted a comprehensive examination of the molecular lipid composition within arterial segments from individuals with CLTI, and with and without diabetes. Our investigations unveiled a striking revelation: the sphingolipid ceramide 18:1/16:0 emerged as the predominant ceramide species that was significantly elevated in the peripheral arterial int...