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TNF ligand related molecule‐1A inhibits atherosclerosis in apoE‐deficient mice
Author(s) -
Zhao Dan,
Yang Xiaoxiao,
Chen Yuanli,
Duan Yajun,
Han Jihong
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.654.13
Subject(s) - osteopontin , chemistry , foam cell , oil red o , apolipoprotein e , vascular smooth muscle , downregulation and upregulation , in vivo , endocrinology , medicine , macrophage , biology , biochemistry , adipose tissue , in vitro , smooth muscle , microbiology and biotechnology , disease , gene , adipogenesis
TNF ligand related molecule‐1A (TL1A) is one of vascular endothelial growth inhibitors. The regulation of neovascularization by TL1A indicates that it may play a vital role in the development of atherosclerosis. However, the exact effect of TL1A on the development of atherosclerosis and the underlying mechanisms, such as the functions of TL1A on foam cell formation and vascular smooth muscle cell (VSMC) phenotype, remain unknown. In this study, we induced atherosclerosis in apoE deficient (apoE −/− ) mice by feeding the animals a high‐fat diet (HFD) while intraperitoneally injecting them recombinant TL1A twice a week, for 12 weeks. After treatment, we collected mouse aorta, serum and liver samples to determine the effect of TL1A on atherosclerotic lesions and fatty liver, and expression of the related molecules. The results of Oil red O, VVG and Alizarin red S staining show that administration of TL1A led to a significant reduction of lesions while enhancing plaque stability. The inhibition of lesions by TL1A was attributed to its effect on formation of foam cells derived from SMCs, but not from macrophages. Corresponding, TL1A activated expression of ABCA1 and ABCG1 in SMCs, but not in macrophages. Both the in vivo and in vitro results showed that TL1A inhibited the transformation of SMCs from contractile phenotype into synthetic one by inducing expression of contractile markers (α smooth muscle actin or αSMA) and inhibiting expression of synthetic marker (osteopontin, OPN). In addition, we determined that TL1A treatment decreased liver triglyceride contents by upregulation of HSL and ATGL expression. Taken together, our work shows that TL1A can inhibit the development of atherosclerosis by regulating SMC/foam cell formation and SMC phenotypes. Our study may also provide a new strategy for atherosclerosis treatment. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .