Circulation. 2002;105:1399-1402
Published online before print February 25, 2002, doi: 10.1161/01.CIR.0000013424.28206.8F
Published online before print February 25, 2002, doi: 10.1161/01.CIR.0000013424.28206.8F
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(Circulation. 2002;105:1399.)
© 2002 American Heart Association, Inc.
High-Density Lipoprotein Restores Endothelial Function in Hypercholesterolemic Men
From Cardiology (L.E.S., I.S., D.H., C.B., R.C., F.R., T.F.L., G.N.), University Hospital, Zürich; and ZLB Central Laboratory (P.G.L, M.G.L.), Blood Transfusion Service, Swiss Red Cross, Berne, Switzerland.
Correspondence to Georg Noll, MD, Cardiology, University Hospital, CH-8091 Zürich, Switzerland. E-mail karnog{at}usz.unizh.ch
Background— Hypercholesterolemia is a risk factor for atherosclerosis-causing endothelial dysfunction, an early event in the disease process. In contrast, high-density lipoprotein (HDL) cholesterol inversely correlates with morbidity and mortality representing a protective effect. Therefore, we investigated the effects of reconstituted HDL on endothelial function in hypercholesterolemic men.
Methods and Results— Endothelium-dependent and -independent vasodilation to intraarterial acetylcholine and sodium nitroprusside (SNP), respectively, was measured by forearm venous occlusion plethysmography in healthy normo- and hypercholesterolemic men. In hypercholesterolemics, the effects of reconstituted HDL (rHDL; 80 mg/kg IV over 4 hours) on acetylcholine- and SNP-induced changes in forearm blood flow were assessed in the presence or absence of the nitric oxide (NO) synthase inhibitor L-NMMA. Hypercholesterolemics showed reduced vasodilation to acetylcholine but not to SNP compared with normocholesterolemics (P<0.0001). rHDL infusion increased plasma HDL cholesterol from 1.3±0.1 to 2.2±0.1 mmol/L (P<0.0001, n=18) and significantly enhanced the acetylcholine-induced increase in forearm blood flow without affecting that induced by SNP. rHDL infusion also improved flow-mediated dilation of the brachial artery (to 4.5±0.9% from 2.7±0.6%, P=0.02). NO synthase inhibition prevented the improvement in acetylcholine-induced vasodilation while leaving the response to SNP unchanged. Albumin infusion in an equivalent protein dose had no effect on vasomotion or lipid levels.
Conclusions— In hypercholesterolemic patients, intravenous rHDL infusion rapidly normalizes endothelium-dependent vasodilation by increasing NO bioavailability. This may in part explain the protective effect of HDL from coronary heart disease and illustrates the potential therapeutic benefit of increasing HDL in patients at risk from atherosclerosis.
Key Words: atherosclerosis • cholesterol • apolipoproteins • nitric oxide • acetylcholine
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