Reduced clusterin (APO J) content of low density lipoproteins contribute to endothelial dysfunction In adiponectin-deficient mice

Abstract

Aim: Low adiponectin and clusterin (apoJ) levels are risk factors of atherosclerosis. The present study aims to investigate the relationships of adiponectin with clusterin in lipoproteins and endothelial dysfunction. Methods: Wild type and adiponectin-deficient mice were fed high fat diet for at least 12 weeks. The recombinant adenoviruses encoding mouse adiponectin or luciferase (as control) were administrated into wild type and adiponectin-deficient mice through tail vein injection. Cholesterol and protein levels were measured in low and high density lipoproteins (LDL and HDL) separated by density gradient ultracentrifugation. Clusterin was detected in LDL and HDL by Western blotting using specific antibody. Vascular function were assessed in wild type and adiponectin-deficient mice using wire myography. Results: Circulating levels of total and LDL-cholesterols were significantly increased in adiponectin-deficient mice by 50.7% and 89.1%, respectively, compared with wild type mice (P < 0.05). Protein/cholesterol ratio in LDL particles was significantly lower in adiponectin-deficient mice than that in wild type mice (0.58±0.10 vs. 0.79±0.02, P < 0.05). Clusterin content in LDL particles were significantly decreased in adiponectin-deficient mice (fold change vs. wild type: 0.35±0.04, P < 0.05). The endothelium-dependent contraction was significantly enhanced in arteries from the adiponectin-deficient mice compared to the wild type controls. The endothelium-dependent relaxation was significantly attenuated by adiponectin deficiency. Treatment of recombinant adenoviruses encoding mouse adiponectin increased clusterin content in LDL by nearly 90% and ameliorated the endothelium-dependent vascular function in adiponectin-deficient mice. Conclusions: Adiponectin may exert anti-atherogenic effects and prevent endothelial dysfunction via its interactions with clusterin in LDL.