β-Migrating Very Low Density Lipoprotein Attenuates Endothelium-Dependent Relaxation in Rabbit Atherosclerotic Aortas

Abstract

We studied the effects of β-migrating very low density lipoprotein (β-VLDL) on the vascular responses of isolated thoracic aortic preparations taken from normal and hypercholesterolemic rabbits. The endothelium-dependent relaxation induced by acetylcholine or adenosine triphosphate (ATP) was attenuated in the arteries from hypercholesterolemic rabbits that were fed a cholesterol-rich diet for 12 weeks. In these aortas, the lesional circumference of the atherosclerotic plaques (fatty streaks) was only 12.18 ± 1.98 %. The relaxation induced by the Ca²⁺ ionophore A23187 or nitroglycerin was not altered. Preincubation with β-VLDL significantly inhibited the relaxation due to acetylcholine, ATP, or A23187, especially in the aortas of hypercholesterolemic rabbits. However, β-VLDL did not alter the response to nitroglycerin. Preincubation with high density lipoprotein had no significant effect on vessel relaxation. These results indicated that endothelium-dependent relaxation was already inhibited in the early stages of atherosclerosis, and that the atherogenic lipoprotein, β -VLDL, further inhibited endothelium-dependent relaxation in atherosclerotic aortas. It may be that β -VLDL also plays a role in determining the level of vascular tonus in atherosclerosis.