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Dietary Cholesterol Supplements Disturb Copper Homeostasis in Multiple Organs in Rabbits: Aorta Copper Concentrations Negatively Correlate with the Severity of Atherosclerotic Lesions

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Abstract

Dietary cholesterol causes atherosclerosis along with a reduction of copper concentrations in the atherosclerosis wall. This study was to determine the relationship between aorta copper concentrations and the severity of atherosclerotic lesions as well as copper homeostasis in multiple organs in cholesterol-fed rabbits. Male New Zealand white rabbits, 10-week-old and averaged 2.0 kg, were fed a diet containing 1% (w/w) cholesterol or the same diet without cholesterol as controls. Twelve weeks after the feeding, aortic atherosclerotic lesions, serum cholesterol, and multiple organ copper concentrations were measured. Compared to controls, rabbits fed cholesterol-supplemented diet displayed higher serum cholesterol levels and developed atherosclerosis. Copper concentrations in the cholesterol-fed rabbits were increased in the serum and kidney but decreased in the atherosclerosis wall and multiple organs, including heart, liver, spleen, and lung. Furthermore, aorta copper concentrations negatively correlated, respectively, with the severity of the atherosclerotic lesion (r = − 0.64, p = 0.01), the microscope atherosclerotic lesion area (r = − 0.60, p = 0.02), and the stenosis of the lumen (r = − 0.54, p = 0.04). Dietary cholesterol not only causes atherosclerosis but also disturbs copper homeostasis in multiple organ systems. The negative correlation between aorta copper concentrations and the severity of atherosclerotic lesions suggests a vicious cycle between copper reduction and the pathogenesis of atherosclerosis. These changes in copper homeostasis would be additive to atherosclerosis as a risk factor for cardiovascular disease in humans.

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Acknowledgements

The authors wish to acknowledge Zhenghui Luo, Jingyao Zhang, and Qipu Feng for their technical assistance and Dr. Ying Xiao for statistically assistance

Funding

This work was supported by West China Hospital of Sichuan University.

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Contributions

Hualin Li: Conceptualization, methodology, data curation, writing—original draft preparation. Lijun Zhao: Conceptualization and experimentation. Tao Wang: Conceptualization and writing—original draft. Y. James Kang: Conceptualization and writing—review and editing

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Correspondence to Y. James Kang.

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The study was approved by the Institutional Animal Care and Use Committee at the Sichuan University West China Hospital, following the guidelines of the US National Institutes of Health. All participants provided the written informed consent.

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Figure S1

Schematic diagram of abdominal aorta sampling. The suprarenal abdominal artery (a) was shown in orange for evaluation of gross atherosclerotic lesion area by Oil Red O stain. The infrarenal abdominal artery segment was cut into several transverse segments. The first segment (b) (1-cm length) was shown in blue for the measurement of plaque copper concentration, the others were shown in yellow (c) (3-mm length per segment, about 6 ~ 8 transverse segments) for histological examination and cross-section quantification of atherosclerotic lesion area (PNG 1058 kb)

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Li, H., Zhao, L., Wang, T. et al. Dietary Cholesterol Supplements Disturb Copper Homeostasis in Multiple Organs in Rabbits: Aorta Copper Concentrations Negatively Correlate with the Severity of Atherosclerotic Lesions. Biol Trace Elem Res 200, 164–171 (2022). https://doi.org/10.1007/s12011-021-02618-0

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