Myocardial infarction differentially alters sphingolipid levels in plasma, erythrocytes and platelets of the rat

Abstract

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.

Fig. 1

The impact of myocardial infarction on the plasma concentration of rat cardiac troponin I (TNNI3, myocardial damage marker). Values from control and sham-operated groups were below the level of detection, and are not shown. Black vertical bars represent SD (n = 6 per group, with the exception of 24 h post-infract, n = 5). a p < 0.001 as compared with 1 h post-infarct group value, b p < 0.05 as compared with 6 h post-infarct group value

Fig. 2

The impact of myocardial infarction (black triangles) or sham operation (open triangles) on the level of sphingosine-1-phosphate (S1P) in blood plasma (A), erythrocytes (B) and platelets (C). Black vertical bars represent SD. When bars not visible, SD is smaller than the size of the marker. a p < 0.05 as compared to the control, b p < 0.05 as compared to appropriate sham group

Fig. 3

The impact of myocardial infarction (black triangles) or sham operation (open triangles) on the level of sphingosine (SPH) in blood plasma (A), erythrocytes (B) and platelets (C). Black vertical bars represent SD. When bars not visible, SD is smaller than the size of the marker. a p < 0.05 as compared to the control, b p < 0.05 as compared to appropriate sham group

Fig. 4

The impact of myocardial infarction (black triangles) or sham operation (open triangles) on the level of dihydrosphingosine (DHS) in blood plasma (A), erythrocytes (B) and platelets (C). Black vertical bars represent SD. When bars not visible, SD is smaller than the size of the marker. a p < 0.05 as compared to the control, b p < 0.05 as compared to appropriate sham group

Fig. 5

The impact of myocardial infarction (black triangles) or sham operation (open triangles) on the level of dihydrosphingosine-1-phosphate (DHS1P) in blood plasma (A), erythrocytes (B) and platelets (C). Black vertical bars represent SD. When bars not visible, SD is smaller than the size of the marker. a p < 0.05 as compared to the control; b p < 0.05 as compared to appropriate sham group

Fig. 6

The impact of myocardial infarction (black triangles) or sham operation (open triangles) on the total level of ceramide (CER) in blood plasma (A), erythrocytes (B) and platelets (C). Black vertical bars represent SD. When bars not visible, SD is smaller than the size of the marker. a p < 0.05 as compared to the control, b p < 0.05 as compared to appropriate sham group

Fig. 7

The impact of myocardial infarction (black triangles) or sham operation (open triangles) on the activity of sphingosine kinase (SK) in erythrocytes (A) and platelets (B). Black vertical bars represent SD (n = 6 per group). a p < 0.05 as compared to the control, b p < 0.05 as compared to appropriate sham group

Fig. 8

The impact of ligation of the left coronary artery, ligation of the femoral artery and second anesthesia on the plasma level of sphingosine (A) dihydrosphingosine (B), sphingosine-1-phosphate (C), dihydrosphingosine-1-phosphate (D) and ceramide (E). The blood samples were taken 6 h after ligation of the arteries and after second anesthesia applied in 6 h after the first one. Values represent mean ± SD. a p < 0.05 as compared to the control

Fig. 9

The impact of ligation of the left coronary artery, ligation of the femoral artery and second anesthesia on the level of sphingosine (A) dihydrosphingosine (B), sphingosine-1-phosphate (C), dihydrosphingosine-1-phosphate (D) and ceramide (E) in erythrocytes. The blood samples were taken 6 h after ligation of the arteries and after second anesthesia applied in 6 h after the first one. Values represent mean ± SD. a p < 0.05 as compared to the control

Fig. 10

The impact of ligation of the left coronary artery, ligation of the femoral artery and second anesthesia on the level of sphingosine (A) dihydrosphingosine (B), sphingosine-1-phosphate (C), dihydrosphingosine-1-phosphate (D) and ceramide (E) in platelets. The blood samples were taken 6 h after ligation of the arteries and after second anesthesia applied in 6 h after the first one. Values represent mean ± SD. a p < 0.05 as compared to the control

Fig. 11

The impact of ligation of the left coronary artery, and ligation of the femoral artery on the activity of sphingosine kinase (SK) in erythrocytes (A) and platelets (B). The blood samples were taken 6 h after ligation of the arteries.Values represent mean ± SD. a p < 0.05 as compared to the control