Induction of endothelin-1 production in endothelial cells via co-operative action between CD40 and lectin-like oxidized LDL receptor (LOX-1).
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), originally identified as the major receptor for oxidized low-density lipoprotein in endothelial cells, mediates the interaction between activated platelets and endothelial cells. Stimulation of LOX-1 causes various functional changes in endothelial cells relevant to 'endothelial dysfunction'. This study investigated the cellular responses to platelet binding via LOX-1, comparing it with CD40, which also mediates platelet-binding in endothelial cells. Activated platelets, which bind both LOX-1 and CD40, induced endothelin-1 production via co-operation of LOX-1 and CD40. Stimulation of LOX-1 by oxidized low-density lipoprotein induced the expression of CD40 as well as LOX-1 itself, and stimulation of CD40 by CD40L induced the expression of LOX-1 as well as CD40. Activated platelets induced both LOX-1 and CD40 expression via these two systems in endothelial cells. Application of superoxide dismutase suppressed LOX-1-mediated, but not CD40-mediated, induction of endothelin-1. LOX-1 and CD40 synergistically, but through a distinct pathway, work to induce endothelin-1 expression in endothelial cells. This co-operative action between LOX-1 and CD40 might play a key role in the induction of endothelial dysfunction.
Sakurai
Kanako
K
Department of Physiology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
Cominacini
Luciano
L
Garbin
Ulisse
U
Fratta Pasini
Anna
A
Sasaki
Noriko
N
Takuwa
Yoh
Y
Masaki
Tomoh
T
Sawamura
Tatsuya
T
D000818:Animals; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010973:Platelet Adhesiveness; D012333:RNA, Messenger / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
D019013:CD40 Antigens; D019332:Endothelin-1; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D013481:Superoxides; D023201:CD40 Ligand; D013482:Superoxide Dismutase