Theranostics 2020; 10(22):10231-10244. doi:10.7150/thno.48410 This issue Cite

Research Paper

Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE-/- mice

Yuna Shang1#, Chuanrui Ma2#, Jing Zhang2, Zhongyan Wang1,4, Chunhua Ren4, Xin Luo1, Rong Peng1, Jingfei Liu1, Jingyuan Mao2, Yang Shi1✉, Guanwei Fan2,3✉

1. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, P. R. China.
2. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300381, P. R. China.
3. State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P. R. China.
4. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, P. R. China.
#These authors contributed equally to this article.

Citation:
Shang Y, Ma C, Zhang J, Wang Z, Ren C, Luo X, Peng R, Liu J, Mao J, Shi Y, Fan G. Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE-/- mice. Theranostics 2020; 10(22):10231-10244. doi:10.7150/thno.48410. https://www.thno.org/v10p10231.htm
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Abstract

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Background and Purpose: Atherosclerosis is vascular disease of chronic inflammation and lipid disorder, which is a major cause of coronary heart disease. Foam cell formation is key progress during the atherosclerosis development. Insulin-like growth factor (IGF)-1 is a growth hormone that plays a crucial role in growth, metabolism, and homeostasis. Previous studies have demonstrated that increase in circulating IGF-1 can reduce atherosclerotic burden. However, active IGF-1 is characterized with poor tissue retention and is at a very low level in circulation system. Therefore, supplementation of exogenous IGF-1 to restore the physiological level is a promising approach to inhibit atherosclerosis. In this study, we develop a self-assembling, anti-inflammatory drug-modified peptide derived from IGF-1 to mimic IGF-1 bioactivity and simultaneously with an anti-inflammatory property for the treatment of atherosclerosis.

Methods: ApoE-/- mice were subcutaneously (s.c.) injected with the different hydrogels or natural IGF-1 protein solution per week and simultaneously fed a high-fat diet for 16 weeks. Atherosclerotic lesion formation and stability were assessed after treatment. Moreover, peritoneal macrophage and serum samples were collected to determine lipid profile and inflammatory cytokines. Concurrently, we determined the effect of bifunctional supramolecular nanofibers/hydrogel on cholesterol efflux, foam cell formation, phenotypic transformation of VSMC to macrophage-like cells, and macrophage polarization in vitro or in vivo.

Results: Bifunctional supramolecular nanofibers/hydrogel for the treatment of atherosclerosis was formed by a short peptide consisting of a tetrapeptide SSSR from C-region of growth factor IGF-1, an anti-inflammatory drug naproxen (Npx), and a powerful self-assembling D-peptide DFDF. The resulting hydrogel of Npx-DFDFGSSSR (Hydrogel 1, H1) possessed both the anti-inflammatory and IGF-1 mimicking properties, and it efficiently promoted the expression of ABCA1 and ABCG1, thereby significantly reducing cholesterol accumulation in macrophages and preventing foam cell formation. Moreover, H1 markedly inhibited the transformation of vascular smooth muscle cells (VSMCs) into macrophage-like cells which also contributed to foam cell formation. In addition, H1 significantly reduced the inflammatory response in vitro and in vivo. Most importantly, the IGF-1 mimetic peptide showed comparable performance to IGF-1 in vivo and inhibited atherosclerosis by markedly reducing lesion area and enhancing plaque stability.

Conclusions: Our study provides a novel supramolecular nanomaterial to inhibit pathological progress of atherosclerosis through regulating cholesterol efflux and inflammation, which may contribute to the development of a promising nanomedicine for the treatment of atherosclerosis in the clinic.

Keywords: IGF-1 mimetic peptide, bifunctional supramolecular nanofiber, cholesterol efflux, foam cells, atherosclerosis, inflammation


Citation styles

APA
Shang, Y., Ma, C., Zhang, J., Wang, Z., Ren, C., Luo, X., Peng, R., Liu, J., Mao, J., Shi, Y., Fan, G. (2020). Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE-/- mice. Theranostics, 10(22), 10231-10244. https://doi.org/10.7150/thno.48410.

ACS
Shang, Y.; Ma, C.; Zhang, J.; Wang, Z.; Ren, C.; Luo, X.; Peng, R.; Liu, J.; Mao, J.; Shi, Y.; Fan, G. Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE-/- mice. Theranostics 2020, 10 (22), 10231-10244. DOI: 10.7150/thno.48410.

NLM
Shang Y, Ma C, Zhang J, Wang Z, Ren C, Luo X, Peng R, Liu J, Mao J, Shi Y, Fan G. Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE-/- mice. Theranostics 2020; 10(22):10231-10244. doi:10.7150/thno.48410. https://www.thno.org/v10p10231.htm

CSE
Shang Y, Ma C, Zhang J, Wang Z, Ren C, Luo X, Peng R, Liu J, Mao J, Shi Y, Fan G. 2020. Bifunctional supramolecular nanofiber inhibits atherosclerosis by enhancing plaque stability and anti-inflammation in apoE-/- mice. Theranostics. 10(22):10231-10244.

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