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Visualization and Inhibition of Mitochondria-Nuclear Translocation of Apoptosis Inducing Factor by a Graphene
Yuhui Sun1, Wen Gao1, Yujie Zhao1
1College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University , Jinan, Shandong 250014, P.R. China.
Abstract:
High concentrations of oxidized low density lipoprotein (oxLDL) induce aberrant apoptosis of vascular smooth muscle cells (VSMCs) in atherosclerotic plaques. This apoptosis cannot be blocked completely by the inhibition of caspase, and it eventually potentiates plaque disruption and risk for cardiovascular disease. Given the important role of apoptosis inducing factor (AIF) in caspase-independent apoptosis, here we develop an AIF-targeting nanosensor by the assembly of graphene oxide (GO) nanosheets and dye-labeled DNA hybrid structures. This nanosensor selectively localizes in the cytosol of VSMCs, where it exhibits a "turn-off" fluorescence signal. Under oxLDL stimuli, the release of AIF from mitochondria into cytosol liberates the DNA hybrid structures from the surface of GO and results in a "turn-on" fluorescence signal. This nanosensor is shown to possess rapid response, high sensitivity, and selectivity for AIF that enables real-time imaging of AIF translocation in VSMCs. Using this novel nanosensor, a better assessment of the apoptotic level of VSMCs and a more accurate evaluation of the extent of atherosclerotic lesions can be obtained. More importantly, the abundant binding between DNA hybrid structures and AIF inhibits the translocation of AIF into the nucleus and subsequent apoptosis in VSMCs. This inhibition may help stabilize plaque and reduce the risk of heart attack and stroke.
Insights
Researchers developed a novel graphene oxide nanosensor to detect apoptosis-inducing factor (AIF) in vascular smooth muscle cells (VSMCs). This tool aids in assessing atherosclerosis and may help prevent cardiovascular disease by inhibiting AIF-mediated apoptosis.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Nanotechnology
Background:
- High oxidized low-density lipoprotein (oxLDL) concentrations trigger caspase-independent apoptosis in vascular smooth muscle cells (VSMCs), contributing to atherosclerotic plaque instability and cardiovascular disease risk.
- Apoptosis-inducing factor (AIF) plays a critical role in this caspase-independent apoptotic pathway, making it a key target for therapeutic and diagnostic interventions.
Purpose of the Study:
- To develop and characterize a novel graphene oxide (GO)-based nanosensor for real-time detection and imaging of AIF translocation in VSMCs.
- To investigate the potential of this nanosensor to assess VSMC apoptosis and atherosclerotic lesion extent.
- To explore the therapeutic potential of the nanosensor in inhibiting AIF-mediated apoptosis and stabilizing atherosclerotic plaques.
Main Methods:
- Assembly of graphene oxide (GO) nanosheets with dye-labeled DNA hybrid structures to create an AIF-targeting nanosensor.
- Characterization of the nanosensor's selective localization in the cytosol of VSMCs and its fluorescence "turn-off" state.
- Monitoring the "turn-on" fluorescence signal upon oxLDL stimulation due to AIF release and subsequent DNA hybrid structure liberation.
- Real-time imaging of AIF translocation and evaluation of AIF-VSMC binding for apoptosis inhibition.
Main Results:
- The developed nanosensor demonstrated rapid response, high sensitivity, and selectivity for AIF, enabling real-time imaging of AIF translocation in VSMCs.
- The nanosensor successfully detected oxLDL-induced AIF release and subsequent VSMC apoptosis.
- Binding of the DNA hybrid structures to AIF effectively inhibited AIF translocation into the nucleus, thereby reducing VSMC apoptosis.
Conclusions:
- The AIF-targeting GO nanosensor provides a powerful tool for accurate assessment of VSMC apoptosis and atherosclerotic lesion progression.
- The nanosensor's ability to inhibit AIF translocation offers a promising therapeutic strategy for plaque stabilization and reducing the risk of cardiovascular events like heart attack and stroke.