RRC ID 12043
Author Hayakawa Y, Hirashima Y, Yamamoto H, Hayashi N, Kurimoto M, Kuwayama N, Endo S.
Title Adenovirus-mediated expression of heparin cofactor II inhibits thrombin-induced cellular responses in fibroblasts and vascular smooth muscle cells.
Journal Thromb Res
Abstract Heparin cofactor II functions as a physiological inhibitor of thrombin activity. The rate of inactivation of thrombin by heparin cofactor II is increased in the presence of dermatan sulfate, which is produced by fibroblasts or smooth muscle cells. To elucidate the role of heparin cofactor II in the extravascular cells, we induced expression of heparin cofactor II in cultured human fibroblasts or vascular smooth muscle cells using adenovirus-mediated gene transfer. After infection of adenovirus vector, these cells secreted heparin cofactor II protein into culture medium. The expressed heparin cofactor II formed the complex with exogenous thrombin and inhibited the proteolytic activity of thrombin. Expression of heparin cofactor II by infection of adenovirus vector inhibited thrombin-induced tissue-type plasminogen activator and interleukin-6 releases from fibroblasts and thrombin-induced interleukin-6 release from vascular smooth muscle cells. These findings show that fibroblasts and vascular smooth muscle cells expressing heparin cofactor II are resistant to thrombin-induced cellular responses.
Volume 116(4)
Pages 357-63
Published 2005-1-1
DOI 10.1016/j.thromres.2005.01.003
PII S0049-3848(05)00034-4
PMID 16038721
MeSH Adenoviridae / genetics* Cells, Cultured Fibroblasts / drug effects* Heparin Cofactor II / administration & dosage Heparin Cofactor II / genetics* Heparin Cofactor II / pharmacology* Humans Interleukin-6 / antagonists & inhibitors Interleukin-6 / metabolism Muscle, Smooth, Vascular / cytology Muscle, Smooth, Vascular / drug effects* Myocytes, Smooth Muscle / drug effects Thrombin / antagonists & inhibitors* Thrombin / pharmacology Tissue Plasminogen Activator / antagonists & inhibitors Tissue Plasminogen Activator / metabolism Transduction, Genetic
IF 2.869
Times Cited 5
DNA material Ax1w1 (RDB1746)