title: Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in LDL receptor-deficient mice.
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.
authors: Department of Pediatrics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
authors: W
authors: W
authors: Zhao
authors: Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China.
authors: T
authors: T
authors: Lei
authors: Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China.
authors: H
authors: H
authors: Li
authors: Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China.
authors: D
authors: D
authors: Sun
authors: Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China.
authors: X
authors: X
authors: Mo
authors: Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China.
authors: Z
authors: Z
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China.
authors: K
authors: K
authors: Zhang
authors: Department of Biochemistry and Molecular Biology, Guiyang Medical University, Guiyang, Guizhou, China.
authors: H
authors: H
authors: Ou
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D005822:Genetic Vectors; D015848:Interleukin-5 / Q000378:metabolism*; D016086:Lentivirus; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D015848:Interleukin-5; D011973:Receptors, LDL