Journal
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
Volume 19, Issue 3, Pages 229-234Publisher
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
DOI: 10.4196/kjpp.2015.19.3.229
Keywords
ICAM-1; Nafamostat mesilate; p66shc; Reactive oxygen species; VCAM-1
Categories
Funding
- Korean Health Technology R&D Project through the Korean Health Industry Development Institute - Ministry of Health & Welfare, Republic of Korea [HI13C1990010013]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2014R1A6A1029617]
- research fund of Chungnam National University
- Chungnam National University Hospital
Ask authors/readers for more resources
Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-alpha (TNF-alpha). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-alpha for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01 similar to 100 mu g/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF- alpha (3 ng/mL), and it dose dependently prevented the TNF- alpha -induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF- alpha -induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF- alpha -induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available