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

Verhamme, Peter ; Quarck, Rozenn ; Hao, Hiroyuki ; Knaapen, Michiel ; Dymarkowski, Steven ; Bernar, Hilde ; Van Cleemput, Johan ; Janssens, Stefan ; Vermylen, Jozef ; Gabbiani, Giulio ; Kockx, Mark ; Holvoet, Paul

In: Cardiovascular Research, 2002, vol. 56, no. 1, p. 135-144

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    Titre
    • Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs
    Auteur
    • Verhamme, Peter. Cardiovascular Research Unit, Center for Experimental Surgery and Anesthesiology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium
    • Quarck, Rozenn. Cardiovascular Research Unit, Center for Experimental Surgery and Anesthesiology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium
    • Hao, Hiroyuki. Department of Pathology, University of Geneva-CMU, Geneva, Switzerland
    • Knaapen, Michiel. AZ-Middelheim and Department of Pharmacology, University of Antwerp, Antwerp, Belgium
    • Dymarkowski, Steven. Department of Radiology, UZ Leuven, Leuven, Belgium
    • Bernar, Hilde. Cardiovascular Research Unit, Center for Experimental Surgery and Anesthesiology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium
    • Van Cleemput, Johan. Department of Cardiology, UZ Leuven, Leuven, Belgium
    • Janssens, Stefan. Department of Cardiology, UZ Leuven, Leuven, Belgium
    • Vermylen, Jozef. Center for Molecular and Vascular Biology, KU Leuven, Belgium
    • Gabbiani, Giulio. Department of Pathology, University of Geneva-CMU, Geneva, Switzerland
    • Kockx, Mark. AZ-Middelheim and Department of Pharmacology, University of Antwerp, Antwerp, Belgium
    • Holvoet, Paul. Cardiovascular Research Unit, Center for Experimental Surgery and Anesthesiology, KU Leuven, Campus Gasthuisberg, O&N, Herestraat 49, B-3000 Leuven, Belgium
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:294147
    Summary
    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-α-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