Volume 87, Issue 5, May (2002), pp. 447-458 © The Author 2002
doi:10.1079/BJN2002555

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Effects of dietary oxysterols on coronary arteries in
hyperlipidaemic hamsters

Alexandra Meynier¹, Jeanine Lherminier², Joelle Demaison-Meloche¹, Christian Ginies³, Andre Grandgirard¹ and Luc Demaison^1,*
INRA, Unité de Nutrition Lipidique, BP 86510, 17 rue Sully, 21065 Dijon, France
INRA, Service Commun de Microscopie, BP 86510, Bretenière, 21065 Dijon, France
INRA, Laboratoire de Recherche sur les Arômes, BP 86510, 17 rue Sully, 21065 Dijon, France

 (Received 30 March 2001–Revised 3 December 2001–Accepted 21 December 2001)

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 (5×10⁻⁶m) was measured and the morphology of coronary arteries was visualized by transmission electron microscopy. Coronary spasm was determined by evaluating reactivity to serotonin (5×10⁻⁶m). 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 (5×10⁻⁶m) 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.

Keywords:
Coronary arteries: Dietary oxysterols: Atherosclerosis: Vasospasm