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(Circulation. 2004;110:3355-3359.)
© 2004 American Heart Association, Inc.

Vascular Medicine

High-Density Lipoprotein Stimulates Myocardial Perfusion In Vivo

Bodo Levkau, MD^*; Sven Hermann, MD^*; Gregor Theilmeier, MD; Markus van der Giet, MD; Jerold Chun, MD, PhD; Otmar Schober, MD; Michael Schäfers, MD

From the Institute of Pathophysiology, Center of Internal Medicine, University Hospital Essen, Essen, Germany (B.L.); Departments of Cardiology and Angiology (B.L.), Nuclear Medicine (S.H., O.S., M.S.), and Anesthesiology (G.T.), University Hospital Münster, Münster, Germany; Medizinische Klinik IV, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany (M.v.d.G.); and Department of Molecular Biology, The Scripps Research Institute, La Jolla, Calif (J.C.).

Correspondence to Bodo Levkau, MD, Institute of Pathophysiology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany. E-mail levkau{at}uni-essen.de

Received January 28, 2004; de novo received April 29, 2004; revision received June 30, 2004; accepted July 6, 2004.

Background— Several clinical studies have demonstrated a close association between plasma HDL cholesterol levels and endothelium-dependent vasodilation in peripheral arteries. In isolated arteries, HDL has been shown to mediate vasodilation via NO release. In vivo, administration of reconstituted HDL restored abnormal endothelial function of the brachial artery in hypercholesterolemic patients. However, no data are currently available on the effect of HDL on myocardial perfusion.

Methods and Results— In this study, administration of human HDL enhanced incorporation of the perfusion tracer ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) into the murine heart in vivo by 18%. This increase was completely abolished in mice deficient for endothelial NO synthase. Because we have recently identified sphingosine 1-phosphate (S1P) as an important vasoactive component contained in HDL, we measured myocardial perfusion after administration of S1P in vivo. We observed an 25% decrease in myocardial MIBI uptake, which was abolished in mice deficient for the S1P receptor S1P₃. In S1P₃^–/– mice, the stimulatory effect of HDL on myocardial perfusion was preserved.

Conclusions— HDL increased myocardial perfusion under basal conditions in vivo via NO-dependent mechanisms, whereas S1P inhibited myocardial perfusion through the S1P₃ receptor. Thus, HDL may reduce coronary risk via direct NO-mediated vasodilatory effects on the coronary circulation.

Key Words: radioisotopes • microcirculation • blood flow • lipoproteins • perfusion

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