Lycopene inhibits cyclic strain-induced endothelin-1 expression through the suppression of reactive oxygen species generation and induction of heme oxygenase-1 in human umbilical vein endothelial cells.
Lycopene is the most potent active antioxidant among the major carotenoids, and its use has been associated with a reduced risk for cardiovascular disease (CVD). Endothelin-1 (ET-1) is a powerful vasopressor synthesized by endothelial cells and plays a crucial role in the pathophysiology of CVD. However, the direct effects of lycopene on vascular endothelial cells have not been fully described. This study investigated the effects of lycopene on cyclic strain-induced ET-1 gene expression in human umbilical vein endothelial cells (HUVECs) and identified the signal transduction pathways that are involved in this process. Cultured HUVECs were exposed to cyclic strain (20% in length, 1 Hz) in the presence or absence of lycopene. Lycopene inhibited strain-induced ET-1 expression through the suppression of reactive oxygen species (ROS) generation through attenuation of p22(phox) mRNA expression and NAD(P)H oxidase activity. Furthermore, lycopene inhibited strain-induced ET-1 secretion by reducing ROS-mediated extrace-llular signal-regulated kinase (ERK) phosphorylation. Conversely, lycopene treatment enhanced heme oxygenase-1 (HO-1) gene expression through the activation of phosphoinositide 3-kinase (PI3K)/Akt pathway, followed by induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation; in addition, HO-1 silencing partially inhibited the repressive effects of lycopene on strain-induced ET-1 expression. In summary, our study showed, for the first time, that lycopene inhibits cyclic strain-induced ET-1 gene expression through the suppression of ROS generation and induction of HO-1 in HUVECs. Therefore, this study provides new valuable insight into the molecular pathways that may contribute to the proposed beneficial effects of lycopene on the cardiovascular system.
Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Li-Chin
LC
Sung
Shin Kong Wu Ho-Su Memorial Hospital, Taipei Medical University, Taipei, Taiwan.|Department of Surgery, School of Medicine, Taipei Medical University, Taipei, Taiwan.
Hung-Hsing
HH
Chao
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Cheng-Hsien
CH
Chen
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Jen-Chen
JC
Tsai
Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Ju-Chi
JC
Liu
School of Chinese Medicine, China Medical University, Taichung, Taiwan.
Hong-Jye
HJ
Hong
Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan.
Tzu-Hurng
TH
Cheng
Graduate Institute of Clinical Medicine, College of Medicine, China Medical University, Taichung, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Jin-Jer
JJ
Chen
D002338:Carotenoids / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D000077276:Lycopene; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013314:Stress, Mechanical
D019332:Endothelin-1; D017382:Reactive Oxygen Species; D002338:Carotenoids; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D000077276:Lycopene
endothelial cells; endothelin-1; heme oxygenase-1; lycopene; reactive oxygen species; strain