HDL and its sphingosine-1-phosphate content in cardioprotection.
Increasing evidence suggests that High-density lipoproteins (HDL) are a direct cardioprotective agent in the setting of acute myocardial ischemia/reperfusion injury, and that this cardioprotection occurs independently of their atheroprotective effect. Studies on the involved mechanisms have revealed that the biologically active HDL-compound sphingosine-1-phosphate (S1P) is responsible for the beneficial effect of HDL on the myocardium. There appears to be an intricate interplay between known preconditioning agents and components of the S1P synthesis machinery in the heart, which makes S1P signalling an attractive downstream convergence point of preconditioning and cardioprotection at the level of its G protein-coupled receptors. While local S1P production has been known to protect the heart against ischemia/reperfusion injury and to mediate preconditioning, systemic S1P supply via HDL adds a novel aspect to the regulation of cardioprotection. Thus the S1P-content of HDL may serve both as a potential cardiovascular risk marker and a novel therapeutic target. Strategies for short-term "acute" HDL elevation as well as S1P analogues may prove beneficial not only in the high-risk patient but also in any patient at risk of myocardial ischemia.
Keul
Petra
P
Institut für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Sattler
Katherine
K
Levkau
Bodo
B
D000208:Acute Disease; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003402:Creatine Kinase; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008075:Lipoproteins, HDL / Q000502:physiology*; D008246:Lysophospholipids / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009206:Myocardium; D017853:Phosphotransferases (Alcohol Group Acceptor); D012307:Risk Factors; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D000099157:Sphingosine Kinase
D003402:Creatine Kinase; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate