Adiponectin attenuates endothelial dysfunction induced by oxidised low-density lipoproteins.
We investigated whether the adipocytokine, adiponectin, protected the endothelium against damage induced by oxidised low-density lipoprotein cholesterol (oxLDL). Human umbilical vein endothelial cells were cultured with either 200 or 350 microg/ml oxLDL, with or without adiponectin purified from human serum (12 microg/ml). Cellular oxidative status was assessed by measuring reactive oxygen species (ROS), peroxynitrite and glutathione (GSH) levels, while cell function was evaluated by measuring nitric oxide (NO) levels and immunohistochemical examination of proteins in the adherens cell junction. At a concentration of 200 microg/ml, oxLDL induced a small increase in ROS and peroxynitrite levels, a two-fold increase in GSH levels and no changes in NO levels or localisation of proteins in the adherens junction. However, 350 microg/ml of oxLDL induced a marked increase in ROS and peroxynitrite levels, a four-fold reduction in GSH levels and a significant decrease in NO levels and disruption of the adherens junctions. Addition of adiponectin to the cultures resulted in maintenance of normal ROS, peroxynitrite and GSH levels, with no change in either NO levels or protein localisation in the adherens junction. This study demonstrates that adiponectin protects against endothelial dysfunction and cellular disruption induced by oxLDL, with this effect being due, in part, to maintenance of intracellular GSH levels.
Lipid and Diabetes Research Group, Christchurch Hospital, Private Bag 4710, Christchurch 8001, New Zealand.
Stuart
S
Plant
Brett
B
Shand
Peter
P
Elder
Russell
R
Scott
D022005:Adherens Junctions / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D048430:Cell Shape; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000099152:Cadherin 5
D052242:Adiponectin; D015703:Antigens, CD; D015820:Cadherins; D005978:Glutathione; D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D030421:Peroxynitrous Acid; D017382:Reactive Oxygen Species; D051176:beta Catenin; D000099152:Cadherin 5; C499918:ADIPOQ protein, human; C495270:CTNNB1 protein, human; C099252:oxidized low density lipoprotein