Nafamostat Mesilate Inhibits TNF-α-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production

• 영문명: Nafamostat Mesilate Inhibits TNF-α-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Min-Woong Kang Hee-Jung Song Shin Kwang Kang Yonghwan Kim Saet-byel Jung Sungju Jee Jae Young Moon K
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제19권 제3호, 229~234쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2015.01.01

영문 초록

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-α (TNF-α). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α 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 mitogenactivated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01∼100 μg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-α (3 ng/mL), and it dose dependently prevented the TNF-α-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-α-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-α-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.

키워드

ICAM-1 Nafamostat mesilate p66shc Reactive oxygen species VCAM-1