title: Ox-Lp(a) transiently induces HUVEC autophagy via an ROS-dependent PAPR-1-LKB1-AMPK-mTOR pathway.
abstract: Oxidised lipoprotein(a) [oxLp(a)] is considered as a more potent arteriosclerotic factor than native Lp(a). However, the molecular mechanisms underlying this potency remain unclear. Reactive oxygen species (ROS) possibly act as intracellular second messengers that participate in autophagy stimulation. In this study, the effect of oxLp(a) on endothelial cell autophagy was determined. The mechanism and effect of autophagy on endothelial cells were also investigated. Results showed that oxLp(a) could induce autophagy depending on the generation of cellular ROS. Superoxide dismutase, an antioxidant, could inhibit oxLp(a)-induced autophagy in human umbilical vascular endothelial cells. Furthermore, poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1)-liver kinase B1 (LKB1)-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) and LKB1-AMPK-mTOR pathways are involved in oxLp(a)-induced autophagy. These pathways are also dependent on ROS. Thus, oxLp(a) induced autophagy via LKB1-AMPK-mTOR and PAPR-1-LKB1-AMPK-mTOR pathways, which are dependent on ROS generation.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China; Department of Pathology, Afﬁliated Hui Zhou Hospital (The Third People's Hospital of Huizhou), Guangzhou Medical University, Huizhou, Guangdong Province 516002, PR China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Lin
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Xing-Lan
authors.initials: XL
authors.lastname: He
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China; The Second Hospital Affiliated to University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Tang
authors.affiliation: The Second Hospital Affiliated to University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Jun-Fa
authors.initials: JF
authors.lastname: Zeng
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Ma
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Lei
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Ren
authors.initials: R
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China.
authors.forename: Dang-Heng
authors.initials: DH
authors.lastname: Wei
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China. Electronic address: zsjianglab@yahoo.cn.
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Jiang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, PR China. Electronic address: smt121101@163.com.
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001161:Arteriosclerosis / Q000503:physiopathology; D001343:Autophagy; D049452:Green Fluorescent Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D017270:Lipoprotein(a) / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017270:Lipoprotein(a); D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D049452:Green Fluorescent Proteins; D013482:Superoxide Dismutase; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases
keywords: Arteriosclerosis; Autophagy; Oxidised lipoprotein(a); Oxygen species