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SHR Neuro Krebs Kardio Lipid

Wu, BJ; Li, Y; Ong, KL; Sun, Y; Shrestha, S; Hou, L; Johns, D; Barter, PJ; Rye, KA.
Reduction of In-Stent Restenosis by Cholesteryl Ester Transfer Protein Inhibition.
ARTERIOSCL THROM VAS. 2017; 37(12): 2333-2341.
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Sun Yidan
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Abstract:
Angioplasty and stent implantation, the most common treatment for atherosclerotic lesions, have a significant failure rate because of restenosis. This study asks whether increasing plasma high-density lipoprotein (HDL) levels by inhibiting cholesteryl ester transfer protein activity with the anacetrapib analog, des-fluoro-anacetrapib, prevents stent-induced neointimal hyperplasia. New Zealand White rabbits received normal chow or chow supplemented with 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Iliac artery endothelial denudation and bare metal steel stent deployment were performed after 2 weeks of des-fluoro-anacetrapib treatment. The animals were euthanized 4 weeks poststent deployment. Relative to control, dietary supplementation with des-fluoro-anacetrapib reduced plasma cholesteryl ester transfer protein activity and increased plasma apolipoprotein A-I and HDL cholesterol levels by 53±6.3% and 120±19%, respectively. Non-HDL cholesterol levels were unaffected. Des-fluoro-anacetrapib treatment reduced the intimal area of the stented arteries by 43±5.6% (P<0.001), the media area was unchanged, and the arterial lumen area increased by 12±2.4% (P<0.05). Des-fluoro-anacetrapib treatment inhibited vascular smooth muscle cell proliferation by 41±4.5% (P<0.001). Incubation of isolated HDLs from des-fluoro-anacetrapib-treated animals with human aortic smooth muscle cells at apolipoprotein A-I concentrations comparable to their plasma levels inhibited cell proliferation and migration. These effects were dependent on scavenger receptor-B1, the adaptor protein PDZ domain-containing protein 1, and phosphatidylinositol-3-kinase/Akt activation. HDLs from des-fluoro-anacetrapib-treated animals also inhibited proinflammatory cytokine-induced human aortic smooth muscle cell proliferation and stent-induced vascular inflammation. Inhibiting cholesteryl ester transfer protein activity in New Zealand White rabbits with iliac artery balloon injury and stent deployment increases HDL levels, inhibits vascular smooth muscle cell proliferation, and reduces neointimal hyperplasia in an scavenger receptor-B1, PDZ domain-containing protein 1- and phosphatidylinositol-3-kinase/Akt-dependent manner. © 2017 American Heart Association, Inc.
Find related publications in this database (using NLM MeSH Indexing)
Angioplasty, Balloon - adverse effects
Angioplasty, Balloon - instrumentation
Animals -
Anticholesteremic Agents - pharmacology
Apolipoprotein A-I - blood
Carrier Proteins - metabolism
Cell Proliferation - drug effects
Cells, Cultured -
Cholesterol Ester Transfer Proteins - antagonists & inhibitors
Cholesterol Ester Transfer Proteins - metabolism
Cholesterol, HDL - blood
Disease Models, Animal -
Humans -
Hyperplasia -
Iliac Artery - drug effects
Iliac Artery - injuries
Iliac Artery - metabolism
Iliac Artery - pathology
Metals -
Muscle, Smooth, Vascular - drug effects
Muscle, Smooth, Vascular - injuries
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - pathology
Myocytes, Smooth Muscle - drug effects
Myocytes, Smooth Muscle - metabolism
Myocytes, Smooth Muscle - pathology
Neointima -
Oxazolidinones - pharmacology
Phosphatidylinositol 3-Kinase - metabolism
Prosthesis Design -
Proto-Oncogene Proteins c-akt - metabolism
Rabbits -
Scavenger Receptors, Class B - metabolism
Signal Transduction - drug effects
Stents -
Time Factors -
Vascular System Injuries - etiology
Vascular System Injuries - metabolism
Vascular System Injuries - pathology
Vascular System Injuries - prevention & control

Find related publications in this database (Keywords)
angioplasty
apolipoprotein A-I
cholesterol ester transfer protein
iliac artery
vascular smooth muscle cell proliferation
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