title: Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs.
abstract: OBJECTIVE
  To study the effect of dietary cholesterol withdrawal on size and composition of LDL-hypercholesterolemia-induced coronary plaques in miniature pigs.
  
  
  METHODS
  Pigs were on normal chow (control group), on a cholesterol-rich diet for 37 weeks (hypercholesterolemic group) or on a cholesterol-rich diet followed by normal chow for 26 weeks (cholesterol withdrawal group). Endothelial function was assessed with quantitative angiography after intracoronary infusion of acetylcholine, plaque load with intra-coronary ultrasound and plaque composition with image analysis of cross-sections. The effect of porcine serum on coronary smooth muscle cell (SMC) function was studied in vitro.
  
  
  RESULTS
  Cholesterol-rich diet caused LDL-hypercholesterolemia, increased plasma levels of oxidized LDL (ox-LDL) and C-reactive protein (CRP), and induced endothelial dysfunction and coronary atherosclerosis. Dietary cholesterol withdrawal lowered LDL, ox-LDL and CRP. It restored endothelial function, did not affect plaque size but decreased lipid, ox-LDL and macrophage content. Smooth muscle cells and collagen accumulated within the plaque. Increased smoothelin-to-alpha-smooth muscle actin ratio indicated a more differentiated SMC phenotype. Cholesterol lowering reduced proliferation and apoptosis. In vitro, hypercholesterolemic serum increased SMC apoptosis and decreased SMC migration compared to non-hypercholesterolemic serum.
  
  
  CONCLUSIONS
  Cholesterol lowering induced coronary plaque stabilization as evidenced by a decrease in lipids, ox-LDL, macrophages, apoptosis and cell proliferation, and an increase in differentiated SMC and collagen. Increased migration and decreased apoptosis of SMC may contribute to the disappearance of the a-cellular core after lipid lowering.
authors.affiliation: Cardiovascular Research Unit, Center for Experimental Surgery and Anesthesiology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.forename: Rozenn
authors.initials: R
authors.lastname: Quarck
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hao
authors.forename: Michiel
authors.initials: M
authors.lastname: Knaapen
authors.forename: Steven
authors.initials: S
authors.lastname: Dymarkowski
authors.forename: Hilde
authors.initials: H
authors.lastname: Bernar
authors.forename: Johan
authors.initials: J
authors.lastname: Van Cleemput
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Jozef
authors.initials: J
authors.lastname: Vermylen
authors.forename: Giulio
authors.initials: G
authors.lastname: Gabbiani
authors.forename: Mark
authors.initials: M
authors.lastname: Kockx
authors.forename: Paul
authors.initials: P
authors.lastname: Holvoet
mesh_terms: D000109:Acetylcholine; D000818:Animals; D017209:Apoptosis; D002097:C-Reactive Protein / Q000378:metabolism; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D002791:Cholesterol, Dietary; D003094:Collagen / Q000378:metabolism; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000178:diet therapy* / Q000378:metabolism; D003331:Coronary Vessels / Q000000981:diagnostic imaging; D004730:Endothelium, Vascular / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging / Q000178:diet therapy / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D013556:Swine, Miniature; D014463:Ultrasonography
chemical_list: D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D003094:Collagen; D002097:C-Reactive Protein; D000109:Acetylcholine