H(2)O(2) accumulation promoting internalization of ox-LDL in early atherosclerosis revealed via a synergistic dual-functional NIR fluorescence probe

利用协同双功能近红外荧光探针揭示H₂O₂积累促进早期动脉粥样硬化中氧化低密度脂蛋白(ox-LDL)内化

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Abstract

The equilibrium of lipid metabolism is critical to sustaining human health. Metabolic disorders often result in a variety of cardiovascular illnesses, especially atherosclerosis. Atherosclerosis is characterized by complicated complications and high mortality. Cholesterol deposition and oxidative stress have been considered as critical mechanisms in the occurrence and progression of atherosclerosis, however, the relationship between oxidative stress and lipid accumulation remains a puzzle in foam cells during the early stages of atherosclerosis development. Hydrogen peroxide (H(2)O(2)) has been reported to participate in various signaling pathways associated with atherosclerotic diseases. Additionally, the excessive intake of oxidized low-density lipoprotein (ox-LDL) leads to cholesterol accumulation and viscosity increasing in foam cells. Therefore, it is critical to investigate the internalization and modification of ox-LDL by H(2)O(2) in foam cells. Herein, we developed a near-infrared, synergistic dual-functional fluorescent probe capable of detecting H(2)O(2) and viscosity simultaneously with high selectivity and sensitivity. Through in situ imaging of H(2)O(2) and viscosity in vivo, we discovered that H(2)O(2) accumulation leads to an increased intake of ox-LDL in the early stages of plaque formation. This finding establishes a new experimental approach and theoretical foundation for the diagnosis and treatment of atherosclerosis, as well as the development of new medications.

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