Abstract 14417: Infusion of Reconstituted High Density Lipoprotein Inhibits Atherosclerosis And In-Stent Restenosis in High Fat High Cholesterol-Fed Rabbits
Background: Reconstituted high density lipoprotein (rHDL) decreased neointimal hyperplasia in the rat carotid artery balloon injury model in our previous experiments. We tried to show whether HDL reconstituted in our group can decrease neointimal hyperplasia and late loss after stenting and atherosclerotic lesion in high fat high cholesterol (HFHC) fed New Zealand White rabbits.
Methods: rHDL was prepared with human plasma-derived apoA-I and soybean phosphatidyl choline by a molar ratio of 1 to 150. The female NZW rabbits were fed with normal chow or 1% high fat high cholesterol (HFHC) diet for 8 weeks. The left carotid artery of rabbits (N= 5-10) was exposed, and 3.0 X 20 mm cobalt chrome stents were delivered to the common iliac arteries, one to each side. The balloon was inflated to 7-9 atm to achieve balloon to artery diameter ratio of 1.5:1. Intravenous administration of rHDL (80mg/kg) was started 4 hrs before the surgery and continued twice a week for 4 weeks. Four weeks later, aortas were isolated to analyze atherosclerotic lesions and iliac arteries with stents were excised to estimate restenosis by calculating late loss using optical coherent tomography (OCT).
Results: OCT revealed that late lumen loss was 28.8 ± 1.3% in the normal chow fed group. It was 35.1 ± 3.9% in HFHC diet group (p<0.005 vs normal chow Gr.) and 26.4 ± 2.2% in the rHDL treated group (p<0.001 vs HFHC Gr.). Restenosis in stented area was significantly inhibited by decrease of inflammation and synthesis of connective tissues including collagens. Multiple coherent anti-Stokes Raman scattering images revealed that numbers and size of lipid droplets in atherosclerotic lesions were significantly reduced in aortic arch from rHDL infused group. Furthermore, multiplex CARS spectrum uncovered that lipid droplets with diverse spectrum in atherosclerotic lesions were changed to homogenous and smaller ones by rHDL infusion. rHDL infusion reduced infiltration of inflammatory cells in atherosclerotic lesions in aorta and liver.
Conclusions: In HFHC fed rabbits, rHDL may affect the atherosclerotic progression by modulating characteristics of lipid droplets in advanced plaques and in-stent restenosis by reducing inflammation and collagen synthesis in stented lesions.
- © 2011 by American Heart Association, Inc.