Abstract 16832: Oxidized LDL and Adiponectin Interact and Regulate the Other’s Respective Functions
Background: Adiponectin (AN) has anti-diabetic, anti-inflammatory, and anti-atherogenic properties. While the anti-diabetic role of AN has been well defined through the study of its receptors, AdipoR1 and R2, the anti-atherogenic mechanism of AN remains poorly understood. On the other hand, it is generally recognized that oxidized low-density lipoprotein (oxLDL) can potentiate the formation of foam cells and induce the inflammatory responses that are believed to be integral for atherogenesis.
Aim: We assessed the hypothesis that AN might directly bind to oxLDL and attenuate its atherogenic action.
Methods: Interactions between oxLDL and AN were examined by means of ELISA. The binding and action of oxLDL were evaluated using CHO cells expressing LOX-1 and by COS-7 cells transfected with oxLDL receptors. Cultured human coronary artery endothelial cells (HCAECs) and THP-1 cells differentiated into macrophages were also employed to assess the inhibitory effects of AN on oxLDL action.
Results: AN selectively bound to oxLDL, but not to native LDL, in a cell-free assay. Although AN inhibited DiI-labeled oxLDL (DiI-oxLDL) uptake by the oxLDL receptor LOX-1, it did not abrogate the uptake of DiI-labeled native LDL uptake by the LDL receptors expressed by COS-7 cells. AN inhibited DiI-oxLDL uptake by another oxLDL receptor, SR-A, in a dose-dependent manner, and inhibited DiI-oxLDL uptake by endothelial cells and macrophages as well. Moreover, AN suppressed oxLDL-dependent signal transduction in LOX-1-expressing CHO cells and was seen to repress oxLDL-induced signaling and endothelin-1 secretion in HCAECs. Examination of the effect of oxLDL on AN function using COS-7 cells transfected with AdipoR revealed that whereas AN could activate AMP-activated protein kinase (AMPK) in these cells, the addition of oxLDL suppressed this.
Conclusions: In conclusion, AN appears to protect cells from oxLDL-induced endothelial cell dysfunction and foam cell formation by disrupting oxLDL binding to its receptors, while oxLDL may interfere with the physiological functions of AN. We postulate that low AN levels enhance oxLDL function to result in the onset of cardiovascular diseases caused by oxLDL.
Author Disclosures: A. Kakino: None. Y. Fujita: None. T. Sawamura: None.
- © 2016 by American Heart Association, Inc.