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Effects of dietary oxysterols on coronary arteries in hyperlipidaemic hamsters

Published online by Cambridge University Press:  09 March 2007

Alexandra Meynier
Affiliation:
INRA, Unité de Nutrition Lipidique, BP 86510, 17 rue Sully, 21065 Dijon, France
Jeanine Lherminier
Affiliation:
INRA, Service Commun de Microscopie, BP 86510, Bretenière, 21065 Dijon, France
Joelle Demaison-Meloche
Affiliation:
INRA, Unité de Nutrition Lipidique, BP 86510, 17 rue Sully, 21065 Dijon, France
Christian Ginies
Affiliation:
INRA, Laboratoire de Recherche sur les Arômes, BP 86510, 17 rue Sully, 21065 Dijon, France
Andre Grandgirard
Affiliation:
INRA, Unité de Nutrition Lipidique, BP 86510, 17 rue Sully, 21065 Dijon, France
Luc Demaison*
Affiliation:
INRA, Unité de Nutrition Lipidique, BP 86510, 17 rue Sully, 21065 Dijon, France
*
*Corresponding author: Dr Luc Demaison, fax +33 380 63 32 23, email [email protected]
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Abstract

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The aim of this study was to evaluate the effect of dietary oxysterols on coronary atherosclerosis and vasospasm. Golden Syrian hamsters were fed three diets with different lipid contents for 3 months: (1) a normolipidaemic diet containing 25 g corn oil–fish oil (4:1, w/w)/kg (group Low L); (2) a hyperlipidaemic diet composed of the normolipidaemic diet supplemented with 150 g lard+30 g cholesterol/kg (group High L); (3) a third diet, similar to the hyperlipidaemic diet, in which 4 g cholesterol/kg was replaced by a mixture of oxysterols (group High L+OS). The oxysterol mixture contained (g/kg): 5,6α-epoxycholesterol 211, 5,6β-epoxycholesterol 179, 7α-hydroxycholesterol 67, 7β-hydroxycholesterol (7βOH) 185, 7-ketocholesterol (7 K) 235; and trace amounts of 7-hydroperoxycholesterols (approximately 30 g/kg). Atherosclerosis was evaluated by measuring myocardial Ca, oxysterols and acyl-CoA cholesterol acyl transferase (ACAT) activity; furthermore, coronary reactivity to sodium nitroprusside (5×10-6 m) was measured and the morphology of coronary arteries was visualized by transmission electron microscopy. Coronary spasm was determined by evaluating reactivity to serotonin (5×10-6 m). Feeding the high-lipid diet (group High L) increased the plasma level of 7βOH, 7 K and cholestanetriol. The presence of oxysterols in the diet (group High L+OS) further increased the concentrations of 7βOH and 7 K in the plasma. However, as evidenced by myocardial Ca, ACAT activity and coronary reactivity to sodium nitroprusside, severe atherosclerosis did not develop during the 3-month diet. 7 K was increased in myocardial lipids of groups High L and High L+OS. Electron microscopy did not show the development of atherosclerosis in group High L, whereas vascular wall thickening, endothelial damage and smooth muscle cell proliferation and migration occurred when oxysterols were present in the food. Serotonin (5×10-6 m) induced exacerbated coronary vasoconstriction in group High L that was completely reversed by dietary oxysterols. In conclusion, dietary oxysterols exhibit anti-spasmodic properties, but they cannot be used as agents against excess dietary lipid-induced coronary spasm because of their atherogenic properties.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2002

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