title: High-density lipoprotein stimulates myocardial perfusion in vivo.
abstract: 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.
  
  
  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 approximately 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 approximately 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.
authors.affiliation: Institute of Pathophysiology, Center of Internal Medicine, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany. levkau@uni-essen.de
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.forename: Sven
authors.initials: S
authors.lastname: Hermann
authors.forename: Gregor
authors.initials: G
authors.lastname: Theilmeier
authors.forename: Markus
authors.initials: M
authors.lastname: van der Giet
authors.forename: Jerold
authors.initials: J
authors.lastname: Chun
authors.forename: Otmar
authors.initials: O
authors.lastname: Schober
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000187:drug effects; D011877:Radionuclide Imaging; D049349:Receptors, Lysosphingolipid / Q000172:deficiency / Q000235:genetics; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000081025:Sphingosine-1-Phosphate Receptors; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics
chemical_list: D008075:Lipoproteins, HDL; D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C501285:S1pr3 protein, mouse; D000081025:Sphingosine-1-Phosphate Receptors; C060506:sphingosine 1-phosphate; D009569:Nitric Oxide; D017256:Technetium Tc 99m Sestamibi; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D013110:Sphingosine