Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Gerhard Pichler

Roland Malli

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

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. Doi: 10.1161/ATVBAHA.117.310051 [OPEN ACCESS]
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Co-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