title: Angiotensin II upregulates endothelial lipase expression via the NF-kappa B and MAPK signaling pathways.
abstract: BACKGROUND
  Angiotensin II (AngII) participates in endothelial damage and inflammation, and accelerates atherosclerosis. Endothelial lipase (EL) is involved in the metabolism and clearance of high density lipoproteins (HDL), the serum levels of which correlate negatively with the onset of cardiovascular diseases including atherosclerosis. However, the relationship between AngII and EL is not yet fully understood. In this study, we investigated the effects of AngII on the expression of EL and the signaling pathways that mediate its effects in human umbilical vein endothelial cells (HUVECs).
  
  
  RESULTS
  HUVECs were cultured in vitro with different treatments as follows: 1) The control group without any treatment; 2) AngII treatment for 0 h, 4 h, 8 h, 12 h and 24 h; 3) NF-κB activation inhibitor pyrrolidine dithiocarbamate (PDTC) pretreatment for 1 h before AngII treatment; and 4) mitogen-activated protein kinase (MAPK) p38 inhibitor (SB203580) pretreatment for 1 h before AngII treatment. EL levels in each group were detected by immunocytochemical staining and western blotting. HUVECs proliferation was detected by MTT and proliferating cell nuclear antigen (PCNA) immunofluorescence staining. NF-kappa B (NF-κB) p65, MAPK p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and phosphorylated extracellular signal-regulated kinase (p-ERK) expression levels were assayed by western blotting. The results showed that the protein levels of EL, NF-κB p65, MAPK p38, JNK, and p-ERK protein levels, in addition to the proliferation of HUVECs, were increased by AngII. Both the NF-kB inhibitor (PDTC) and the MAPK p38 inhibitor (SB203580) partially inhibited the effects of AngII on EL expression.
  
  
  CONCLUSIONS
  AngII may upregulate EL protein expression via the NF-κB and MAPK signaling pathways.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital, Jinan, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Wu
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital, Jinan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Morphology Laboratory, School of Medicine, Shandong University, Jinan, China.
authors.forename: Qingli
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Gaowa
authors.initials: G
authors.lastname: Saren
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Diagnostics, School of Medicine, Shandong University, Jinan, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Meng
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yue
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008049:Lipase / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D011759:Pyrrolidines; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D000804:Angiotensin II; C020972:pyrrolidine dithiocarbamic acid; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C410382:LIPG protein, human; D008049:Lipase; C093642:SB 203580