title: Inhibition of autophagy ameliorates atherogenic inflammation by augmenting apigenin-induced macrophage apoptosis.
abstract: Increasing evidences showed that the survival of macrophages promotes atherogenesis. Macrophage apoptosis in the early phase of atherosclerotic process negatively regulates the progression of atherosclerotic lesions. We demonstrated that a natural anti-oxidant apigenin could ameliorate atherogenesis in ApoE(-/-) mice. It reduced the number of foam cells and decreased the serum levels of tumor necrosis factor α, interleukin 1β (IL-1β) and IL-6. Our results showed that oxidized low-density lipoprotein (oxLDL) led to the secretion of pro-inflammatory cytokines. Apigenin-induced apoptosis and downregulated the secretion of TNF-α, IL-6 and IL-1β. It is further supported by the use of zVAD, a pan-caspase inhibitor, demonstrating that apigenin lowered cytokine profile through induction of macrophage apoptosis. Moreover, apigenin-induced Atg5/Atg7-dependent autophagy in macrophages pretreated with oxLDL. Results illustrated that autophagy inhibition increased apigenin-induced apoptosis through activation of Bax. The present findings suggest that oxLDL maintained the survival of macrophages and activated the secretion of pro-inflammatory cytokines to initiate atherosclerosis. Apigenin-induced apoptosis of lipid-laden macrophages and resolved inflammation to ameliorate atherosclerosis. In conclusion, combination of apigenin with autophagy inhibition may be a promising strategy to induce foam cell apoptosis and subdue atherogenic cytokines.
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Wen
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China; Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China. Electronic address: 13480405@life.hkbu.edu.hk.
authors.forename: Xiuqiong
authors.initials: X
authors.lastname: Fu
authors.affiliation: The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China; Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: sxg_smu@126.com.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D047310:Apigenin / Q000008:administration & dosage* / Q000009:adverse effects; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000008:administration & dosage; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D009842:Oligopeptides; D051028:bcl-2-Associated X Protein; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; C099252:oxidized low density lipoprotein; D047310:Apigenin
keywords: Apigenin; Apoptosis; Autophagy; Cytokines; Macrophages; Oxidized low-density lipoprotein