Pharmacological inhibition of C-C chemokine receptor 4 aggravates atherosclerosis through prevention of regulatory T cell recruitment to the lesions
| Autor: | K Hirata, Shoji Kawauchi, Sayo Horibe, Naoto Sasaki, Yoshiyuki Rikitake, Hilman Zulkifli Amin |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | European Heart Journal. 41 |
| ISSN: | 1522-9645 0195-668X |
| DOI: | 10.1093/ehjci/ehaa946.3727 |
| Popis: | Background Regulatory T cells (Tregs) are demonstrated to play a protective role in the development of atherosclerosis. However, their sites of action in atherosclerosis remain unclear. Although C-C chemokine receptor 4 (CCR4) has been shown to contribute to the accumulation of Tregs in inflamed tissues and prevention of experimental autoimmune diseases, the role of CCR4 in Treg migration to atherosclerotic lesions and suppression of plaque formation remains unknown. Methods and results We intraperitoneally injected 8-week-old apolipoprotein E–deficient mice fed a normal diet with vehicle (n=9) or a 4-μg dose of a CCR4 antagonist (n=10) 3 times weekly for 8 weeks and evaluated atherosclerotic lesions at 16 weeks old. Administration of the CCR4 antagonist significantly aggravated atherosclerotic plaque formation (aortic sinus plaque area: 2.91±0.87×104 μm2 versus 5.41±0.98×104 μm2 in control vehicle-treated and CCR4 antagonist-treated mice, respectively; P Conclusions Our findings indicate an important role for CCR4 in promotion of Treg recruitment into atherosclerotic lesions and subsequent prevention of early atherosclerosis and suggest CCR4 as a novel therapeutic target for atherosclerosis. Funding Acknowledgement Type of funding source: None |
| Databáze: | OpenAIRE |
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