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Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in LDL receptor-deficient mice

Gene Therapy volume 22, pages 645–652 (2015)Cite this article

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Abstract

Interleukin-5 (IL-5) increases the secretion of natural T15/EO6 IgM antibodies that inhibit the uptake of oxidized low-density lipoprotein (LDL) by macrophages. This study aimed to determine whether macrophage-specific expression of IL-5 in LDL receptor-deficient mice (Ldlr−/−) could improve cholesterol metabolism and reduce atherosclerosis. To induce macrophage-specific IL-5 expression, the pLVCD68-IL5 lentivirus was delivered into Ldlr−/− mice via bone marrow transplantation. The recipient mice were fed a Western-type diet for 12 weeks to induce lesion formation. We found that IL-5 was efficiently and specifically overexpressed in macrophages in recipients of pLVCD68-IL5-transduced bone marrow cells (BMC). Plasma titers of T15/EO6 IgM antibodies were significantly elevated by 58% compared with control mice transplanted with pLVCD68 lacking the IL-5 coding sequence. Plaque areas of aortas in IL-5-overexpressing mice were reduced by 43% and associated with a 2.4-fold decrease in lesion size at the aortic roots when compared with mice receiving pLVCD68-transduced BMCs. The study showed that macrophage-specific overexpression of IL-5 inhibited the progression of atherosclerotic lesions. These findings suggest that modulation of IL-5 cytokine expression represents a potential strategy for intervention of familial hypercholesterolemia and other cardiovascular diseases.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81460277).

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Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China

    W Zhao

  2. Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China

    T Lei, H Li, D Sun, X Mo, Z Wang, K Zhang & H Ou

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Correspondence to H Ou.

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Zhao, W., Lei, T., Li, H. et al. Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in LDL receptor-deficient mice. Gene Ther 22, 645–652 (2015). https://doi.org/10.1038/gt.2015.33

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