© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs
aCardiovascular Research Unit, Center for Experimental Surgery and Anesthesiology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium
bDepartment of Pathology, University of Geneva–CMU, Geneva, Switzerland
cAZ-Middelheim and Department of Pharmacology, University of Antwerp, Antwerp, Belgium
dDepartment of Radiology, UZ Leuven, Leuven, Belgium
eDepartment of Cardiology, UZ Leuven, Leuven, Belgium
fCenter for Molecular and Vascular Biology, KU Leuven, Belgium
* Corresponding author. Tel.: +32-16-347-149; fax: +32-16-347-114 paul.holvoet{at}med.kuleuven.ac.be
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-
-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.
KEYWORDS Atherosclerosis; Cholesterol; Endothelial function; Lipoproteins; Smooth muscle
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