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<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 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.
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<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 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.
Authors: Julian C van Capelleveen; Andrea E Bochem; M Mahdi Motazacker; G Kees Hovingh; John J P Kastelein Journal: Curr Atheroscler Rep Date: 2013-06 Impact factor: 5.113
Authors: Panagiotis Fotakis; Vishal Kothari; David G Thomas; Marit Westerterp; Matthew M Molusky; Elissa Altin; Sandra Abramowicz; Nan Wang; Yi He; Jay W Heinecke; Karin E Bornfeldt; Alan R Tall Journal: Arterioscler Thromb Vasc Biol Date: 2019-10-03 Impact factor: 8.311
Authors: C Roger White; Geeta Datta; Landon Wilson; Mayakonda N Palgunachari; G M Anantharamaiah Journal: Chem Phys Lipids Date: 2019-01-29 Impact factor: 3.329