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Vinexin β ablation inhibits atherosclerosis in apolipoprotein E-deficient mice by inactivating the akt-nuclear factor jB inflammatory axis
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نویسنده
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guan h. ,cheng w.-l. ,guo j. ,chao m.-l. ,zhang y. ,gong j. ,zhu x.-y. ,she z.-g. ,huang z. ,li h.
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منبع
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journal of the american heart association - 2017 - دوره : 6 - شماره : 2
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چکیده
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Background-vinexin β is a novel adaptor protein that regulates cellular adhesion,cytoskeletal reorganization,signal transduction,and transcription; however,the exact role that vinexin β plays in atherosclerosis remains unknown. methods and results-immunoblot analysis showed that vinexin β expression is upregulated in the atherosclerotic lesions of both patients with coronary heart disease and hyperlipemic apolipoprotein e-deficient mice and is primarily localized in macrophages indicated by immunofluorescence staining. the high-fat diet-induced double-knockout mice exhibited lower aortic plaque burdens than apolipoprotein e-/- littermates and decreased macrophage content. vinexin β deficiency improved plaque stability by attenuating lipid accumulation and increasing smooth muscle cell content and collagen. moreover,the bone marrow transplant experiment demonstrated that vinexin β deficiency exerts atheroprotective effects in hematopoietic cells. consistent with these changes,the mrna expression of proinflammatory cytokines were downregulated in vinexin β-/- apolipoprotein e-/- mice,whereas the anti-inflammatory m2 macrophage markers were upregulated. the immunohistochemical staining and in vitro experiments showed that deficiency of vinexin β inhibited the accumulation of monocytes and the migration of macrophages induced by tumor necrosis factor α-stimulated human umbilical vein endothelial cells as well as macrophage proliferation. finally,the inhibitory effects exerted by vinexin β deficiency on foam cell formation,nuclear factor κb activation,and inflammatory cytokine expression were largely reversed by constitutive akt activation,whereas the increased expression of the nuclear factor jb subset promoted by adenoviral vinexin β was dramatically suppressed by inhibition of akt. conclusions-vinexin β deficiency attenuates atherogenesis primarily by suppressing vascular inflammation and inactivating akt-nuclear factor κb signaling. our data suggest that vinexin β could be a therapeutic target for the treatment of atherosclerosis. © 2017 the authors.
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کلیدواژه
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AKT; Atherosclerosis; Inflammation; Vinexin β
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آدرس
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department of cardiology,renmin hospital of wuhan university,wuhan,china,cardiovascular research institute,wuhan university,wuhan,china,hubei key laboratory of cardiology,wuhan, China, department of cardiology,renmin hospital of wuhan university,wuhan,china,the institute of model animals of wuhan university,wuhan,china,medical research institute,school of medicine,wuhan university,wuhan, China, department of cardiology,renmin hospital of wuhan university,wuhan,china,the institute of model animals of wuhan university,wuhan,china,medical research institute,school of medicine,wuhan university,wuhan, China, key laboratory of cvd,nanjing medical university,nanjing, China, department of cardiology,renmin hospital of wuhan university,wuhan,china,the institute of model animals of wuhan university,wuhan,china,medical research institute,school of medicine,wuhan university,wuhan, China, department of cardiology,renmin hospital of wuhan university,wuhan,china,the institute of model animals of wuhan university,wuhan,china,medical research institute,school of medicine,wuhan university,wuhan, China, department of cardiology,renmin hospital of wuhan university,wuhan,china,the institute of model animals of wuhan university,wuhan,china,medical research institute,school of medicine,wuhan university,wuhan, China, department of cardiology,renmin hospital of wuhan university,wuhan,china,the institute of model animals of wuhan university,wuhan,china,medical research institute,school of medicine,wuhan university,wuhan, China, college of life science,wuhan university,wuhan, China, department of cardiology,renmin hospital of wuhan university,wuhan,china,the institute of model animals of wuhan university,wuhan,china,medical research institute,school of medicine,wuhan university,wuhan, China
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Authors
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