Lipids and Endothelium-Dependent Vasodilation

Sammanfattning: Impaired endothelium-dependent vasodilation (EDV) is associated with atherosclerotic cardiovascular disease as well as several of its risk factors. The aim of the present thesis was to investigate how lipids influence EDV in the vascular bed of the human forearm. Apolipoprotein B was inversely associated with both EDV and endothelium-independent vasodilation (EIDV) in healthy subjects aged 20-69 years. HDL cholesterol was associated with the EDV to EIDV ratio (EFI). Small LDL particles and antibodies against oxidized LDL were not associated with endothelial vasodilatory function. The EFI in young, healthy subjects was positively associated with alpha-linolenic acid proportion, but inversely associated with myristic acid in men only. Eicosapentaenoic acid was positively associated with EDV, whereas dihomo-gamma-linolenic acid was inversely associated with both EDV and EIDV in men. Acute elevation of long-chain fatty acids with Intralipid®/heparin infusion in young, healthy subjects impaired EDV after 2 h. This impairment could be prevented by co-infusing vitamin C, diclophenac or L-arginine. Acute elevation of both medium-chain and long-chain fatty acids during Structolipid®/heparin infusion did not impair EDV. An ordinary meal (34 E% fat) transiently attenuated EDV at 1 hour. No attenuation in EDV was observed after meals containing 20 and 3 E% fat. These findings show that the endothelial vasodilatory function is associated with fatty acid profile in serum in the fasting state and during acute fatty acid elevation, as well as with apolipoprotein B and HDL cholesterol. Furthermore, lowering dietary fat content to 20 E% or less preserves endothelial vasodilatory function and might therefore protect against atherosclerosis.