Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits |
| |
| Affiliation: | 1. Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy;2. Department of Food and Drug, University of Parma, Parma, Italy;3. NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany;1. State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China;2. Xinjiang Key Laboratory of Cardiovascular Disease Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, China;3. College of Pharmacy, Xinjiang Medical University, Urumqi, China;4. Baker Heart and Diabetes Institute, Melbourne, Australia;5. Xinjiang Key Laboratory of Medical Animal Model Research, Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, China;1. School of Rehabilitation Science, McMaster University, Hamilton, Ontario, Canada;2. Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada;3. McMaster Physical Activity Centre of Excellence, Hamilton, Ontario, Canada;4. St Joseph’s Healthcare Centre London, Western University, London, Ontario, Canada;1. Division of Cardiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA;2. Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada;1. Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada;2. BC Centre for Improved Cardiovascular Health, Vancouver, British Columbia, Canada;3. Division of Cardiology and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada;4. Canadian Vigour Centre, University of Alberta, Edmonton, Alberta, Canada;5. Division of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada |
| |
| Abstract: | BackgroundAmong strategies to reduce the remaining risk of cardiovascular disease, interest has focused on using infusions of synthetic high-density lipoprotein (sHDL).MethodsNew Zealand rabbits underwent a perivascular injury at both carotids and were randomly allocated into 2 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 4 groups of rabbits were treated 5 times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque changes were analysed in vivo by intravascular ultrasound. Blood was drawn from rabbits for biochemical analyses and cholesterol efflux capacity evaluation.ResultsIn both protocols, atheroma volume in the Placebo groups increased between the first and the second intravascular ultrasound evaluation. A stabilization or a slight regression was instead observed vs baseline in the TN-sHDL-treated groups (P < 0.005 vs Placebo after infusion). TN-sHDL treatment caused a sharp rise of plasma-free cholesterol levels and a significant increase of total cholesterol efflux capacity. Histologic analysis of carotid plaques showed a reduced macrophage accumulation in TN-sHDL-treated rabbits compared with Placebo (P < 0.05).ConclusionsOur results demonstrate that acute and subacute treatments with TN-sHDL are effective in stabilizing atherosclerotic plaques in a rabbit model. This effect appears to be related to a reduced intraplaque accumulation of inflammatory cells. Besides recent failures in proving its efficacy, sHDL treatment remains a fascinating therapeutic option for the reduction of cardiovascular risk. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
