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Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs.

AbstractOBJECTIVE:
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.
AuthorsPeter Verhamme, Rozenn Quarck, Hiroyuki Hao, Michiel Knaapen, Steven Dymarkowski, Hilde Bernar, Johan Van Cleemput, Stefan Janssens, Jozef Vermylen, Giulio Gabbiani, Mark Kockx, Paul Holvoet
JournalCardiovascular research (Cardiovasc Res) Vol. 56 Issue 1 Pg. 135-44 (Oct 2002) ISSN: 0008-6363 [Print] England
PMID12237174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cholesterol, Dietary
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Collagen
  • C-Reactive Protein
  • Acetylcholine
Topics
  • Acetylcholine
  • Animals
  • Apoptosis
  • C-Reactive Protein (metabolism)
  • Cell Division
  • Cell Movement
  • Cells, Cultured
  • Cholesterol, Dietary
  • Collagen (metabolism)
  • Coronary Disease (diagnostic imaging, diet therapy, metabolism)
  • Coronary Vessels (diagnostic imaging)
  • Endothelium, Vascular (metabolism)
  • Extracellular Matrix (metabolism)
  • Hypercholesterolemia (diagnostic imaging, diet therapy, metabolism)
  • Lipoproteins, LDL (blood)
  • Models, Animal
  • Muscle, Smooth, Vascular (pathology)
  • Swine, Miniature
  • Ultrasonography

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