dihydrosphingosine-1-phosphate and Myocardial-Infarction

Three bioactive sphingolipids, namely sphingosine-1-phosphate (S1P), ceramide (CER) and sphingosine (SPH) were shown to be involved in ischemia/reperfusion injury of the heart. S1P is a powerful cardioprotectant, CER activates apoptosis and SPH in a low dose is cardioprotective whereas in a high dose is cardiotoxic. The aim of the present study was to examine effects of experimental myocardial infarction on the level of selected sphingolipids in plasma, erythrocytes and platelets in the rat. Myocardial infarction was produced in male Wistar rats by ligation of the left coronary artery. Blood was taken from the abdominal aorta at 1, 6 and 24 h after the ligation. Plasma, erythrocytes and platelets were isolated and S1P, dihydrosphingosine-1-phosphate (DHS1P), SPH, dihydrosphingosine (DHS) and CER were quantified by means of an Agilent 6460 triple quadrupole mass spectrometer using positive ion electrospray ionization source with multiple reaction monitoring. The infarction reduced the plasma level of S1P, DHS1P, SPH and DHS but increased the level of total CER. In erythrocytes, there was a sharp elevation in the level of SPH and DHS early after the infarction and a reduction after 24 h whereas the level of S1P, DHS1P and total CER gradually increased. In platelets, the level of each of the examined compounds profoundly decreased 1 and 6 h after the infarction and partially normalized in 24 h. The results obtained clearly show that experimental heart infarction in rats produces deep changes in metabolism of sphingolipids in the plasma, platelets and erythrocytes.

Topics: Anesthesia; Animals; Ceramides; Coronary Vessels; Erythrocyte Count; Femoral Artery; Ligation; Lysophospholipids; Male; Myocardial Infarction; Phosphotransferases (Alcohol Group Acceptor); Platelet Count; Rats; Rats, Wistar; Sphingolipids; Sphingosine; Troponin T

The sphingolipid sphingosine-1-phosphate (S1P) plays an important role in protecting the heart against ischemia-reperfusion injury. S1P is normally present in human plasma. However, there are no data available on the effect of myocardial infarction on the plasma concentrations of S1P and related sphingolipids. The aim of this study was to examine the concentrations of S1P, sphinganine-1-phosphate, free sphingosine, free sphinganine, and ceramide in the plasma of patients after myocardial infarction.. The study was performed on two groups of male subjects: controls with no specific complaints (n=21) and patients who had had acute myocardial infarction (n=22). In the latter group, blood was taken immediately after admission to the hospital and five days later. The concentrations of the above compounds were measured by high-pressure liquid chromatography.. The concentrations of S1P and sphinganine-1-phosphate were reduced by ca. 50% both early after infarction and five days later. The concentrations of the other compounds were not affected by myocardial infarction.. The reduction in plasma concentration of S1P after infarction could lessen its protective action on cardiomyocyte viability. The observed reduction in S1P level might be associated with the standard antiplatelet treatment given to patients since thrombocytes are one of the major sources of plasma S1P.

Topics: Aged; Animals; Ceramides; Humans; Lysophospholipids; Male; Mice; Middle Aged; Myocardial Infarction; Myocytes, Cardiac; Receptors, Lysosphingolipid; Reperfusion Injury; Sphingosine; Thrombolytic Therapy