Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs.
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.
Verhamme
Peter
P
Cardiovascular Research Unit, Center for Experimental Surgery and Anesthesiology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, Leuven, Belgium.
Quarck
Rozenn
R
Hao
Hiroyuki
H
Knaapen
Michiel
M
Dymarkowski
Steven
S
Bernar
Hilde
H
Van Cleemput
Johan
J
Janssens
Stefan
S
Vermylen
Jozef
J
Gabbiani
Giulio
G
Kockx
Mark
M
Holvoet
Paul
P
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
D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D003094:Collagen; D002097:C-Reactive Protein; D000109:Acetylcholine