Recombinant HDLMilano exerts greater anti-inflammatory and plaque stabilizing properties than HDLwild-type

Abstract Objective The aim of this study was to compare the effects of HDL Milano and HDL wild-type , on regression and stabilization of atherosclerosis. Methods Atherosclerotic New Zealand White rabbits received 2 infusions, 4 days apart, of HDL Milano (75mg/kg of apoA-I Milano ), HDL wild-type (75mg/kg apoA-I wild-type ) or placebo. Pre- and post-treatment plaque volume was assessed by MRI. Markers of plaque vulnerability and inflammation were evaluated. Liver and aortic cholesterol content, aortic ABCA-1 and liver SR-BI were quantified. The effect of apoA-I Milano and wild-type proteins on MCP-1 and COX-2 expression by macrophages was evaluated in vitro. Results Both forms of HDL induced aortic plaque regression (−4.1% and −2.6% vs. pre-treatment in HDL Milano and HDL wild-type respectively, p p =0.009). A similar reduction in cholesterol content of aorta and liver was observed with both treatments vs. placebo. The expression of aortic ABCA-1 and hepatic SR-BI was significantly higher in both treated groups vs. placebo. A significantly reduced plaque macrophage density was observed in the HDL Milano vs. both HDL wild-type and placebo groups. Plaque levels of COX-2, MCP-1, Caspase-3 antigen and MMP-2 activity were significantly reduced in the HDL Milano vs. both HDL wild-type and placebo groups. In vitro studies showed that apoA-I Milano protein significantly reduced expression of COX-2 and MCP-1 in oxLDL loaded macrophages vs. apoA-I wild-type . Conclusions Despite a similar effect on acute plaque regression, the infusion of HDL Milano exerts superior anti-inflammatory and plaque stabilizing effects than HDL wild-type in the short term.