Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice

Objective: Uremia markedly increases the risk of atherosclerosis. Thus, effective anti-atherogenic treatments are needed for uremic patients. This study examined effects of non-lipidated recombinant human apoA-I (h-apoA-I) and a recombinant trimeric apoA-I molecule (TripA-I) on lipid metabolism and atherosclerosis in uremic apoE-/- mice. Methods and results: Upon intraperitoneal injection, h-apoA-I and TripA-I rapidly associated with plasma HDL and reduced mouse apoA-I plasma levels without affecting total or HDL cholesterol concentrations. The plasma half-life was similar to 36 h for TripA-I and similar to 16 h for h-apoA-I. Injection of h-apoA-I (100 mg/kg) or TripA-I (100 mg/kg) twice weekly for 7 weeks did not affect the cross-sectional area of atherosclerotic lesions in the aortic root, or the en face lesion area and cholesterol content in the thoracic aorta in uremic apoE-/- mice. Also, the treatments 4 did not affect expression of selected inflammatory genes in the thoracic aorta or plasma concentrations of soluble ICAM-I and VCAM-1. However, h-apoA-l-treated mice had larger smooth muscle cell-staining areas in aortic root plaques than PBS-treated mice (4.8 +/- 0.8% vs. 2.5 +/- 0.6%, P < 0.05). Conclusions: The data suggest that long-term treatment with non-lipidated h-apoA-I or TripA-I might affect plaque composition but does not reduce atherosclerotic lesion size in uremic apoE-/- mice. (C) 2008 Elsevier Ireland Ltd. All rights reserved.