Role of Ox-LDL/LOX-1/NF-κB signaling pathway in regulation of atherosclerotic plaque growth by testosterone in male rabbits

Objective: The purpose of our study is to investigate the role of oxidized low density lipoprotein (Ox-LDL)/lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1)/nuclear factor-kappa B (NF-kappa B) signaling pathway in the regulation of atherosclerotic plaque growth by testosterone in male atherosclerotic rabbits. Methods: The male rabbit model was prepared by castration and feeding cholesterol-rich diet. Pathological sections of thoracic aorta were performed hematoxylin-eosin staining to observe aortic morphological changes. Total serum testosterone was measured with chemical luminescent method. Serum Ox-LDL, soluble intercellular adhesion molecule-1 (sICAM-1) and matrix metalloproteinases-2 (MMP2) were assayed using ELISA kit following the manufacturer's instructions. Serum tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL6) were assayed using radioimmunoassay. Expressions of LOX-1 of thoracic aorta were measured by RT-PCR, immunohistochemistry and Western blot methods respectively. Results: There was no significant difference in Ox-LDL level between all groups. The LOX-1 mRNA and protein expression of thoracic aorta were significantly higher in the castrated rabbits as compared with the sham-operated ones, and testosterone replacement could reduce the mRNA and protein expression of LOX-1 of thoracic aorta in the castrated rabbits. PIA reduced artery intima thickness and plaque area in castrated rabbits, which was further enhanced by testosterone replacement. PDTC reduced artery intima thickness and plaque area in castrated rabbits, which couldn't be enhanced by testosterone replacement. Conclusions: Our study demonstrates that testosterone can regulate atherosclerotic plaque progression, affect expression of LOX-1 and NF-kappa B in thoracic aorta and play a role in atherosclerotic plaque growth via NF-kappa B rather than Ox-LDL or LOX-1 in male rabbits. (C) 2012 Elsevier Inc. All rights reserved.