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Adiponectin attenuates endothelial dysfunction induced by oxidised low-density lipoproteinsLipid and Diabetes Research Group, Christchurch Hospital, Private Bag 4710, Christchurch 8001, New Zealand.
Lipid and Diabetes Research Group, Christchurch Hospital, Private Bag 4710, Christchurch 8001, New Zealand.
Canterbury Health Laboratories, Christchurch Hospital, Private Bag 4710, Christchurch 8001, New Zealand.
Lipid and Diabetes Research Group, Christchurch Hospital, Private Bag 4710, Christchurch 8001, New Zealand. 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 µg/ml oxLDL, with or without adiponectin purified from human serum (12 µg/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 µg/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 µg/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.
Key Words: adiponectin adherens junction endothelial cells glutathione lipoproteins oxygen radicals
Diabetes and Vascular Disease Research, Vol. 5, No. 2,
102-108 (2008) |
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