Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis

Wen Gao,Wenhua Cao,Bo Tang,Michelle Cai,Zhenhua Liu,Guanwei Cui,Yujie Zhao,Yuhui Sun

doi:10.1038/s41467-017-02657-z

Abstract

Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. Although activation of TRPV1 cation channels by capsaicin may reduce lipid storage and the formation of atherosclerotic lesions, a clinical use for capsaicin has been limited by its chronic toxicity. Here we show that coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells (VSMCs) using near-infrared light. Upon irradiation, local increases of temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx. The increase in intracellular Ca2+ activates autophagy and impedes foam cell formation in VSMCs treated with oxidized low-density lipoprotein. In vivo, CuS-TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid storage and plaque formation in ApoE−/− mice fed a high-fat diet, with no obvious long-term toxicity. Together, this suggests CuS-TRPV1 may represent a therapeutic tool to locally and temporally attenuate atherosclerosis.

Highlights

Atherosclerosis is characterized by the accumulation of lipids within the arterial wall
The successful fabrication of CuS-transient receptor potential vanilloid subfamily 1 (TRPV1) was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE, Supplementary Fig. 2) and fourier transform infrared spectroscopy (FT-IR, Supplementary Fig. 3)
Atherosclerosis is an inflammatory disease that is initiated by lipid-mediated vascular inflammation of the vessel wall, which promotes the formation of vascular smooth muscle cells (VSMCs)/Mφ-derived foam cells

Summary

Introduction

Atherosclerosis is characterized by the accumulation of lipids within the arterial wall. CuS-TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid storage and plaque formation in ApoE−/− mice fed a high-fat diet, with no obvious long-term toxicity Together, this suggests CuS-TRPV1 may represent a therapeutic tool to locally and temporally attenuate atherosclerosis. The increased cytosolic Ca2+ leads to subsequent autophagy activation, which upregulates ABCA1mediated cholesterol efflux and reduces lipid accumulation and foam cell formation in oxLDL-treated VSMCs. Importantly, CuSTRPV1 is able to provide obvious structural PA imaging of cardiac vasculature, making it feasible for precise temporal and spatial control of TRPV1-signaling in vivo. After 12 weeks of PA image-guided therapy, lipid storage and atherosclerotic lesions are significantly reduced in aortic arch of apolipoprotein E knockout (ApoE−/−) mice on a high-fat diet without noticeable in vivo long-term toxicity These results greatly motivate the application of CuS-TRPV1 as a therapeutic tool to attenuate

Methods

Results

Conclusion