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      Moxibustion at CV4 alleviates atherosclerotic lesions through activation of the LXRα/ABCA1 pathway in apolipoprotein-E-deficient mice

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          Abstract

          Objectives:

          To investigate the anti-atherogenic effect of moxibustion and whether it is mediated through the reverse cholesterol transport process.

          Methods:

          8-week-old male apolipoprotein E deficient (ApoE −/− knockout) mice were randomly divided into two groups (n=10 per group): atherosclerosis (AS) and AS plus moxibustion (AS+M). C57BL/6J mice of the same background (n=10) were selected as controls. Mice in the AS+M group received indirect moxibustion with an ignited moxa stick held over CV4. Mice of the AS and control groups were restrained in the same holder with an unlit moxa stick held over CV4. All treatments were performed for 20 min per day, 6 days per week for 12 weeks. After the treatment, the mice were euthanased and their serum lipids were measured. The aortic roots and thoracic aortas were collected for haematoxylin and eosin and red oil O staining, respectively, to analyse the atherosclerotic lesions. Expression of adenosine triphosphate binding cassette (ABCA)A1/G1 and liver X receptor α (LXRα) in the thoracic aorta were examined with Western blotting.

          Results:

          The moxibustion-treated (AS+M) mice showed a significantly lower plaque area percentage in the aortic root and thoracic aorta, and higher expression of LXRα and ABCA1 in the thoracic aorta compared with the AS mice. No significant differences were found in average lipid area percentage in the thoracic aorta, or ABCG1 expression in the thoracic aorta, between mice in the AS+M and AS groups.

          Conclusion:

          Moxibustion treatment at CV4 suppressed the progression of atherosclerotic lesions in ApoE −/− mice. The anti-atherogenic effect of moxibustion may be achieved by: (1) regulation of lipid metabolism, and thus prevention of lipid accumulation; and (2) upregulation of LXRα- and ABCA1-mediated cholesterol efflux in the lesion area.

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          Most cited references18

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          ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation.

          Here we demonstrate that the ABC transporter ABCG1 plays a critical role in lipid homeostasis by controlling both tissue lipid levels and the efflux of cellular cholesterol to HDL. Targeted disruption of Abcg1 in mice has no effect on plasma lipids but results in massive accumulation of both neutral lipids and phospholipids in hepatocytes and in macrophages within multiple tissues following administration of a high-fat and -cholesterol diet. In contrast, overexpression of human ABCG1 protects murine tissues from dietary fat-induced lipid accumulation. Finally, we show that cholesterol efflux to HDL specifically requires ABCG1, whereas efflux to apoA1 requires ABCA1. These studies identify Abcg1 as a key gene involved in both cholesterol efflux to HDL and in tissue lipid homeostasis.
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            ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.

            Initial description of apolipoprotein (apo) E-deficient transgenic mice demonstrated the development of severe hypercholesterolemia due to probable delayed clearance of large atherogenic particles from the circulation. Examination of these mice demonstrated foam cell accumulation in the aortic root and pulmonary arteries by 10 weeks of age. In the present study, the animals were fed either chow or a high-fat, Western-type diet and examined at ages ranging from 6 to 40 weeks. Gross examination by dissection microscopy revealed a predilection for development of lesions in the aortic root, at the lesser curvature of the aortic arch, the principal branches of the aorta, and in the pulmonary and carotid arteries. Monocyte attachment to endothelial cells was observed by light and electron microscopic examination at 6 weeks, the earliest time point examined. Foam cell lesions developed as early as 8 weeks, and after 15 weeks advanced lesions (fibrous plaques) were observed. The latter consisted of a fibrous cap containing smooth muscle cells surrounded by connective tissue matrix that covered a necrotic core with numerous foamy macrophages. Mice fed the Western-type diet generally had more advanced lesions than those fed a chow diet. The apoE-deficient mouse contains the entire spectrum of lesions observed during atherogenesis and is the first mouse model to develop lesions similar to those in humans. This model should provide numerous opportunities to study the pathogenesis and therapy of atherosclerosis in a small, genetically defined animal.
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              The macrophage foam cell as a target for therapeutic intervention.

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                Author and article information

                Journal
                Acupunct Med
                Acupunct Med
                AIM
                spaim
                Acupuncture in Medicine
                SAGE Publications (Sage UK: London, England )
                0964-5284
                1759-9873
                29 May 2019
                August 2019
                : 37
                : 4
                : 237-243
                Affiliations
                [1 ]Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
                [2 ]Acupuncture and Moxibustion Department, Huguosi Hospital of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
                [3 ]School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China
                Author notes
                [*]Baixiao Zhao, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China. Email: baixiao100@ 123456vip.sina.com
                Author information
                https://orcid.org/0000-0002-7922-8707
                Article
                10.1136_acupmed-2016-011317
                10.1136/acupmed-2016-011317
                7433780
                31140825
                01e2486d-1d0a-4d4a-abd1-78c6ec611a82
                © The Author(s) 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 31 December 2017
                Categories
                Original Papers

                Complementary & Alternative medicine
                moxibustion,atherosclerosis,lipid metabolism,cholesterol efflux,reverse cholesterol transport

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