Recombinant HDLMᵢₗₐₙₒ exerts greater anti-inflammatory and plaque stabilizing properties than HDLwᵢₗd₋ₜyₚₑ
2012
Ibanez, Borja | Giannarelli, Chiara | Cimmino, Giovanni | Santos-Gallego, Carlos G. | Alique, Matilde | Pinero, Antonio | Vilahur, Gemma | Fuster, Valentin | Badimon, Lina | Badimon, Juan J.
OBJECTIVE: The aim of this study was to compare the effects of HDLMᵢₗₐₙₒ and HDLwᵢₗd₋ₜyₚₑ, on regression and stabilization of atherosclerosis. METHODS: Atherosclerotic New Zealand White rabbits received 2 infusions, 4 days apart, of HDLMᵢₗₐₙₒ (75mg/kg of apoA-IMᵢₗₐₙₒ), HDLwᵢₗd₋ₜyₚₑ (75mg/kg apoA-Iwᵢₗd₋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 HDLMᵢₗₐₙₒ and HDLwᵢₗd₋ₜyₚₑ respectively, p<0.001 and 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 HDLMᵢₗₐₙₒ vs. both HDLwᵢₗd₋ₜyₚₑ and placebo groups. Plaque levels of COX-2, MCP-1, Caspase-3 antigen and MMP-2 activity were significantly reduced in the HDLMᵢₗₐₙₒ vs. both HDLwᵢₗd₋ₜyₚₑ and placebo groups. In vitro studies showed that apoA-IMᵢₗₐₙₒ protein significantly reduced expression of COX-2 and MCP-1 in oxLDL loaded macrophages vs. apoA-Iwᵢₗd₋ₜyₚₑ. CONCLUSIONS: Despite a similar effect on acute plaque regression, the infusion of HDLMᵢₗₐₙₒ exerts superior anti-inflammatory and plaque stabilizing effects than HDLwᵢₗd₋ₜyₚₑ in the short term.
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