Published Online
on November 15, 2004

A more recent version of this article appeared on November 23, 2004

This Article Full Text (PDF) All Versions of this Article: 110/21/3355    most recent 01.CIR.0000147827.43912.AEv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Levkau, B. Articles by Schäfers, M. Search for Related Content PubMed PubMed Citation Articles by Levkau, B. Articles by Schäfers, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB NITRIC OXIDE Related Collections Imaging Nuclear cardiology and PET PET and SPECT Lipid and lipoprotein metabolism Endothelium/vascular type/nitric oxide

Submitted on January 28, 2004
Revised on June 30, 2004
Accepted on July 6, 2004

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, and 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.).

^* To whom correspondence should be addressed. E-mail: levkau{at}uni-essen.de.

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

This article has been cited by other articles:

				N. K. Hudson, M. O'Hara, H. A. Lacey, J. Corcoran, D. G. Hemmings, M. Wareing, P. Baker, and M. J. Taggart Modulation of Human Arterial Tone During Pregnancy: The Effect of the Bioactive Metabolite Sphingosine-1-Phosphate Biol Reprod, July 1, 2007; 77(1): 45 - 52. [Abstract] [Full Text] [PDF]

				P. Xia Letter by Xia Regarding Article, "High-Density Lipoproteins and Their Constituent, Sphingosine-1-Phosphate, Directly Protect the Heart Against Ischemia/Reperfusion Injury In Vivo via the S1P3 Lysophospholipid Receptor" Circulation, April 10, 2007; 115(14): e393 - e393. [Full Text] [PDF]

				G. Theilmeier, C. Schmidt, J. Herrmann, P. Keul, M. Schafers, I. Herrgott, J. Mersmann, J. Larmann, S. Hermann, J. Stypmann, et al. Response to Letter Regarding Article, "High-Density Lipoproteins and Their Constituent, Sphingosine-1-Phosphate, Directly Protect the Heart Against Ischemia/Reperfusion Injury In Vivo via the S1P3 Lysophospholipid Receptor" Circulation, April 10, 2007; 115(14): e394 - e394. [Full Text] [PDF]

				L. Stegger, A.-N. Hoffmeier, K. P. Schafers, S. Hermann, O. Schober, M. A. Schafers, and G. Theilmeier Accurate Noninvasive Measurement of Infarct Size in Mice with High-Resolution PET J. Nucl. Med., November 1, 2006; 47(11): 1837 - 1844. [Abstract] [Full Text] [PDF]

				G. Theilmeier, C. Schmidt, J. Herrmann, P. Keul, M. Schafers, I. Herrgott, J. Mersmann, J. Larmann, S. Hermann, J. Stypmann, et al. High-Density Lipoproteins and Their Constituent, Sphingosine-1-Phosphate, Directly Protect the Heart Against Ischemia/Reperfusion Injury In Vivo via the S1P3 Lysophospholipid Receptor Circulation, September 26, 2006; 114(13): 1403 - 1409. [Abstract] [Full Text] [PDF]

				C. Mineo, H. Deguchi, J. H. Griffin, and P. W. Shaul Endothelial and Antithrombotic Actions of HDL Circ. Res., June 9, 2006; 98(11): 1352 - 1364. [Abstract] [Full Text] [PDF]

				C. Mineo and P. W. Shaul Circulating cardiovascular disease risk factors and signaling in endothelial cell caveolae Cardiovasc Res, April 1, 2006; 70(1): 31 - 41. [Abstract] [Full Text] [PDF]

				L. Stegger, K. P. Schafers, U. Flogel, L. Livieratos, S. Hermann, C. Jacoby, P. Keul, E. M. Conway, O. Schober, J. Schrader, et al. Monitoring Left Ventricular Dilation in Mice with PET J. Nucl. Med., September 1, 2005; 46(9): 1516 - 1521. [Abstract] [Full Text] [PDF]

				M. Tolle, B. Levkau, P. Keul, V. Brinkmann, G. Giebing, G. Schonfelder, M. Schafers, K. v. W. Lipinski, J. Jankowski, V. Jankowski, et al. Immunomodulator FTY720 Induces eNOS-Dependent Arterial Vasodilatation via the Lysophospholipid Receptor S1P3 Circ. Res., April 29, 2005; 96(8): 913 - 920. [Abstract] [Full Text] [PDF]