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Research Article

Regulation of the macrophage-related inflammatory microenvironment for atherosclerosis treatment and angiogenesis via anti-cytokine agents

Hongji Pu1,§, Minghua Yao2,§, Zhaoyu Wu1,§, Zhijue Xu1,§, Chaoyi Cui1( ), Renhua Huang3, Muhammad Shafiq4, Weimin Li1, Xinwu Lu1( ), Bo Li1( )
Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200040, China
Department of Radiation, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Department of Chemical Engineering, Faculty of Engineering, Graduate School, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan

§ Hongji Pu, Minghua Yao, Zhaoyu Wu, and Zhijue Xu contributed equally to this work.

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Graphical Abstract

Mesoporous silica nanoparticles (MSNs)@anti-IL-1β were able to specifically accumulate in the atherosclerotic plaque, diminish atherosclerotic plaques, and promote angiogenesis to improve ischemia in mice. The anti-cytokine agents may have broad implications in clinical practice for the reduction of the atherosclerosis progression and alleviation of the ischemia.

Abstract

Macrophages-mediated atherosclerosis (AS) is an inflammatory disease and the most common cause of ischemia. With the progress of basic and clinical research, anti-cytokine therapy has garnered considerable attention of the research community for the regulation of the inflammatory microenvironment for AS treatment. Despite of their promising potential, primary clinical trials have revealed that anti-cytokine drugs exhibit poor selectivity and thus affect other parts of the immune system, especially during long-term management. To circumvent these limitations, herein we exploited mesoporous silica nanoparticles (MSNs) with a pore size of 15.5 nm as carriers for the anti-interleukin-1β (anti-IL-1β) delivery to be the anti-cytokine agents. In vitro mechanistic studies indicated that the MSNs@anti-IL-1β can regulate the macrophage-related inflammatory microenvironment, promote the viability of vascular endothelial cells (vECs), and reduce proliferation and phenotypic switching of vascular smooth muscle cells (vSMCs). In vivo evaluation further revealed that the MSNs@anti-IL-1β were preferentially accumulated in macrophages, impeding the AS progress by maintaining the endothelium integrity and inhibiting the vSMCs proliferation. Besides, MSNs@anti-IL-1β induced neovascularization and improved hindlimb ischemia regeneration. Taken together, these MSNs affording the sustained release of anti-cytokine agents may have broad implications for the clinical management of the AS, including the reduction of the AS progression and alleviation of the ischemia.

Keywords

atherosclerosisinflammatory responsenanocarriersmacrophageendothelial cells

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References

1

Pasternak, R. C.; Criqui, M. H.; Benjamin, E. J.; Fowkes, F. G. R.; Isselbacher, E. M.; McCullough, P. A.; Wolf, P. A.; Zheng, Z. J. Atherosclerotic vascular disease conference: Writing group I: Epidemiology. Circulation 2004, 109, 2605–2612.
Crossref Google Scholar
2

Mitchell, G. F.; Guo, C. Y.; Benjamin, E. J.; Larson, M. G.; Keyes, M. J.; Vita, J. A.; Vasan, R. S.; Levy, D. Cross-sectional correlates of increased aortic stiffness in the community: The framingham heart study. Circulation 2007, 115, 2628–2636.
Crossref Google Scholar
3

Herrington, W.; Lacey, B.; Sherliker, P.; Armitage, J.; Lewington, S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ. Res. 2016, 118, 535–546.
Crossref Google Scholar
4

Catapano, A. L.; Graham, I.; De Backer, G.; Wiklund, O.; Chapman, M. J.; Drexel, H.; Hoes, A. W.; Jennings, C. S.; Landmesser, U.; Pedersen, T. R. et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias: The task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European association for cardiovascular prevention & rehabilitation (EACPR). Atherosclerosis 2016, 253, 281–344.
Crossref Google Scholar
5

Aboyans, V.; Ricco, J. B.; Bartelink, M. L. E. L.; Björck, M.; Brodmann, M.; Cohnert, T.; Collet, J. P.; Czerny, M.; De Carlo, M.; Debus, S. et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries Endorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur. Heart J. 2018, 39, 763–816.
Crossref Google Scholar
6

Michos, E. D.; McEvoy, J. W.; Blumenthal, R. S. Lipid management for the prevention of atherosclerotic cardiovascular disease. N. Engl. J. Med. 2019, 381, 1557–1567.
Crossref Google Scholar
7

Wolf, D.; Ley, K. Immunity and inflammation in atherosclerosis. Circ. Res. 2019, 124, 315–327.
Crossref Google Scholar
8

Faxon, D. P.; Fuster, V.; Libby, P.; Beckman, J. A.; Hiatt, W. R.; Thompson, R. W.; Topper, J. N.; Annex, B. H.; Rundback, J. H.; Fabunmi, R. P. et al. Atherosclerotic vascular disease conference: Writing group III: Pathophysiology. Circulation 2004, 109, 2617–2625.
Crossref Google Scholar
9

Hansson, G. K. Immune mechanisms in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2001, 21, 1876–1890.
Crossref Google Scholar
10

Libby, P. Inflammation in atherosclerosis. Nature 2002, 420, 868–874.
Crossref Google Scholar
11

Gimbrone, M. A. Jr. García-Cardeña, G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ. Res. 2016, 118, 620–636.
Crossref Google Scholar
12

Khurana, R.; Zhuang, Z. W.; Bhardwaj, S.; Murakami, M.; De Muinck, E.; Yla-Herttuala, S.; Ferrara, N.; Martin, J. F.; Zachary, I.; Simons, M. Angiogenesis-dependent and independent phases of intimal hyperplasia. Circulation 2004, 110, 2436–2443.
Crossref Google Scholar
13

Li, X. D.; Hong, M. N.; Chen, J.; Lu, Y. Y.; Ye, M. Q.; Ma, Y.; Zhu, D. L.; Gao, P. J. Adventitial fibroblast-derived vascular endothelial growth factor promotes vasa vasorum-associated neointima formation and macrophage recruitment. Cardiovasc. Res. 2020, 116, 708–720.
Crossref Google Scholar
14

Ridker, P. M. From CANTOS to CIRT to COLCOT to clinic: Will all atherosclerosis patients soon be treated with combination lipid-lowering and inflammation-inhibiting agents. Circulation 2020, 141, 787–789.
Crossref Google Scholar
15

Ridker, P. M.; Everett, B. M.; Thuren, T.; MacFadyen, J. G.; Chang, W. H.; Ballantyne, C.; Fonseca, F.; Nicolau, J.; Koenig, W.; Anker, S. D. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 2017, 377, 1119–1131.
Crossref Google Scholar
16

Rossi-Semerano, L.; Fautrel, B.; Wendling, D.; Hachulla, E.; Galeotti, C.; Semerano, L.; Touitou, I.; Koné-Paut, I. Tolerance and efficacy of off-label anti-interleukin-1 treatments in France: A nationwide survey. Orphanet J. Rare Dis. 2015, 10, 19.
Crossref Google Scholar
17

Zhang, J.; Zu, Y. J.; Dhanasekara, C. S.; Li, J.; Wu, D. Y.; Fan, Z. Y.; Wang, S. Detection and treatment of atherosclerosis using nanoparticles. WIREs Nanomed. Nanobiotechnol. 2017, 9, e1412.
Google Scholar
18

Guan, S. Q.; Liu, X. J.; Fu, Y.; Li, C. L.; Wang, J. X.; Mei. Q. X.; Deng, G. Y.; Zheng, W. R.; Wan, Z. P.; Lu, J. A biodegradable “Nano-donut” for magnetic resonance imaging and enhanced chemo/photothermal/chemodynamic therapy through responsive catalysis in tumor microenvironment. J. Colloid Interface Sci. 2022, 608, 344–354.
Crossref Google Scholar
19

Liu, H.; Wang, J. J. Loading IR820 using multifunctional dendrimers with enhanced stability and specificity. Pharmaceutics 2018, 10, 77.
Crossref Google Scholar
20
Ma, Y. ; Xu, L. ; Yin, B. L. ; Shang, J. H. ; Chen, F. F. ; Xu, J. T. ; Song, Z. L. ; Nan, B. ; Song, G. S. ; Zhang, X. B. Ratiometric semiconducting polymer nanoparticle for reliable photoacoustic imaging of pneumonia-induced vulnerable atherosclerotic plaque in vivo. Nano Lett. 2021, 21, 4484–4493.
21

Koga, J. I.; Matoba, T.; Egashira, K. Anti-inflammatory nanoparticle for prevention of atherosclerotic vascular diseases. J. Atheroscler. Thromb. 2016, 23, 757–765.
Crossref Google Scholar
22

Tang, F. Q.; Li, L. L.; Chen, D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater. 2012, 24, 1504–1534.
Crossref Google Scholar
23

Weber, C.; Noels, H. Atherosclerosis: Current pathogenesis and therapeutic options. Nat. Med. 2011, 17, 1410–1422.
Crossref Google Scholar
24

Yan, W.; Jiang, S. Immune cell-derived exosomes in the cancer-immunity cycle. Trends Cancer 2020, 6, 506–517.
Crossref Google Scholar
25

Tabas, I.; Bornfeldt, K. E. Macrophage phenotype and function in different stages of atherosclerosis. Circ. Res. 2016, 118, 653–667.
Crossref Google Scholar
26

Ying, W.; Cheruku, P. S.; Bazer, F. W.; Safe, S. H.; Zhou, B. Y. Investigation of macrophage polarization using bone marrow derived macrophages. J. Vis. Exp. 2013, 76, 50323.
Crossref Google Scholar
27

Zhang, X.; Jiang, Y. H.; Huang, Q.; Wu, Z. Y.; Pu, H. J.; Xu, Z. J.; Li, B.; Lu, X. W.; Yang, X. R.; Qin, J. B. et al. Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia. Stem Cell Res. Ther. 2021, 12, 403.
Crossref Google Scholar
28

Dinarello, C. A. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat. Rev. Rheumatol. 2019, 15, 612–632.
Crossref Google Scholar
29

Grebe, A.; Hoss, F.; Latz, E. NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ. Res. 2018, 122, 1722–1740.
Crossref Google Scholar
30

Grehan, J. F.; Levay-Young, B. K.; Fogelson, J. L.; François-Bongarçon, V.; Benson, B. A.; Dalmasso, A. P. IL-4 and IL-13 induce protection of porcine endothelial cells from killing by human complement and from apoptosis through activation of a phosphatidylinositide 3-kinase/Akt pathway. J. Immunol. 2005, 175, 1903–1910.
Crossref Google Scholar
31

Weinstock, A.; Rahman, K.; Yaacov, O.; Nishi, H.; Menon, P.; Nikain, C. A.; Garabedian, M. L.; Pena, S.; Akbar, N.; Sansbury, B. E. et al. Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis. eLife 2021, 10, e67932.
Crossref Google Scholar
32

Gomez, D.; Baylis, R. A.; Durgin, B. G.; Newman, A. A. C.; Alencar, G. F.; Mahan, S.; St Hilaire, C.; Müller, W.; Waisman, A.; Francis, S. E. et al. Interleukin-1β has atheroprotective effects in advanced atherosclerotic lesions of mice. Nat. Med. 2018, 24, 1418–1429.
Crossref Google Scholar
33

Uhrin, P.; Wang, D. D.; Mocan, A.; Waltenberger, B.; Breuss, J. M.; Tewari, D.; Mihaly-Bison, J.; Huminiecki, Ł.; Starzyński, R. R.; Tzvetkov, N. T. et al. Vascular smooth muscle cell proliferation as a therapeutic target. Part 2: Natural products inhibiting proliferation. Biotechnol. Adv. 2018, 36, 1608–1621.
Crossref Google Scholar
34

Hirano, S.; Zhou, Q.; Furuyama, A.; Kanno, S. Differential regulation of IL-1β and IL-6 release in murine macrophages. Inflammation 2017, 40, 1933–1943.
Crossref Google Scholar
35

Libby, P.; Warner, S. J.; Friedman, G. B. Interleukin 1: A mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J. Clin. Invest. 1988, 81, 487–498.
Crossref Google Scholar
36

Spiliotis, E. T.; Nakos, K. Cellular functions of actin- and microtubule-associated septins. Curr. Biol. 2021, 31, R651–R666.
Crossref Google Scholar
37

Libby, P.; Rocha, V. Z. All roads lead to IL-6: A central hub of cardiometabolic signaling. Int. J. Cardiol. 2018, 259, 213–215.
Crossref Google Scholar
38

Apostolakis, S.; Vogiatzi, K.; Amanatidou, V.; Spandidos, D. A. Interleukin 8 and cardiovascular disease. Cardiovasc. Res. 2009, 84, 353–360.
Crossref Google Scholar
39

González-Navajas, J. M.; Law, J.; Nguyen, K. P.; Bhargava, M.; Corr, M. P.; Varki, N.; Eckmann, L.; Hoffman, H. M.; Lee, J.; Raz, E. Interleukin 1 receptor signaling regulates DUBA expression and facilitates Toll-like receptor 9-driven antiinflammatory cytokine production. J. Exp. Med. 2010, 207, 2799–2807.
Crossref Google Scholar
40

Eelen, G.; De Zeeuw, P.; Simons, M.; Carmeliet, P. Endothelial cell metabolism in normal and diseased vasculature. Circ. Res. 2015, 116, 1231–1244.
Crossref Google Scholar
Nano Research
Volume 15 Issue 8,
August 2022
Pages 7342-7354
DOI: 10.1007/s12274-022-4366-7
Cite this article:
Pu H, Yao M, Wu Z, et al. Regulation of the macrophage-related inflammatory microenvironment for atherosclerosis treatment and angiogenesis via anti-cytokine agents. Nano Research, 2022, 15(8): 7342-7354. https://doi.org/10.1007/s12274-022-4366-7
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Nano biology

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Received: 19 December 2021
Revised: 26 March 2022
Accepted: 28 March 2022
Published: 04 May 2022
© Tsinghua University Press 2022
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