Infusions of large synthetic HDL containing trimeric apoA-I stabilize atherosclerotic plaques in hypercholesterolemic rabbits

ABSTRACT Background Among strategies to reduce the remaining risk of cardiovascular disease, interest has focused on using infusions of synthetic HDL (sHDL). Methods New Zealand rabbits underwent a perivascular injury at both carotids and were randomly allocated into two protocols: 1) a single dose study, where rabbits were treated with a single infusion of sHDL containing a trimeric form of human apoA-I (TN-sHDL, 200 mg/kg) or with Placebo; 2) a multiple dose study, where four groups of rabbits were treated five times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque changes were analysed in vivo by IntraVascular UltraSound (IVUS). Blood was drawn from rabbits for biochemical analyses and cholesterol efflux capacity (CEC) evaluation. Results In both protocols, atheroma volume in the Placebo groups increased between the first and the second IVUS evaluation. A stabilization or a slight regression was instead observed vs baseline in the TN-sHDL treated groups (p Conclusions Our results demonstrate that acute and sub-acute treatments with TN-sHDL are effective in stabilizing atherosclerotic plaques in a rabbit model. This effect appears to be related to a reduced intra-plaque accumulation of inflammatory cells. Besides recent failures in proving its efficacy, sHDL treatment remains a fascinating therapeutic option for reduction of cardiovascular risk.