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).

METHODS AND FINDINGS:

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.

CONCLUSION:

AngII may upregulate EL protein expression via the NF-κB and MAPK signaling pathways.

• Authors: Xiaoli Zhang, Minghui Wu, Hong Jiang, Jing Hao, Qingli Zhang, Qing Zhu, Gaowa Saren, Yun Zhang, Xiaohui Meng, Xin Yue
• Journal: PloS one (PLoS One) Vol. 9 Issue 9 Pg. e107634 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25250890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Imidazoles
• Pyridines
• Pyrrolidines
• Thiocarbamates
• Transcription Factor RelA
• Angiotensin II
• pyrrolidine dithiocarbamic acid
• Extracellular Signal-Regulated MAP Kinases
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• LIPG protein, human
• Lipase
• SB 203580

Topics

• Angiotensin II (pharmacology)
• Blotting, Western
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Imidazoles (pharmacology)
• JNK Mitogen-Activated Protein Kinases
• Lipase (metabolism)
• MAP Kinase Signaling System (drug effects)
• Microscopy, Fluorescence
• Pyridines (pharmacology)
• Pyrrolidines (pharmacology)
• Thiocarbamates (pharmacology)
• Time Factors
• Transcription Factor RelA (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)