Heparin decreases serum sphingosine-1-phosphate levels in patients with vascular diseases.

Abstract

BACKGROUND AND AIMS: Sphingosine-1-phosphate (S1P) is crucial for cardiovascular homeostasis and pathophysiology. We aimed to explore i) whether the associations between blood components and circulating S1P change in patients with atherosclerosis undergoing invasive vascular procedures and ii) whether in a mice model of vascular injury heparin treatment regulates circulatory S1P levels and intimal hyperplasia. METHODS: In a group of patients with vascular diseases, S1P blood concentrations and laboratory parameters were measured before and shortly after vascular procedures (n&#xa0;=&#xa0;330) as well as 3-month later (n&#xa0;=&#xa0;167). We further investigated in C57/Bl6J mice the effect of heparin treatment on serum S1P and intimal hyperplasia after clamping of the abdominal aorta. RESULTS: In patients, perioperative circulating S1P serum concentrations correlated with counts of thrombocytes, leukocytes, neutrophils and lymphocytes, while postoperative S1P concentrations were increasingly linked to erythrocytes counts as well as cholesterol, fibrinogen and calcium levels. Median serum S1P levels dropped by 23&#xa0;% (p&#xa0;<&#xa0;0.0001) after interventions and recovered to the initial levels within 3 months. However, patients under 3-month low molecular weight heparin medication presented with lower S1P concentrations than patients without (p&#xa0;<&#xa0;0.001). In mice, a single heparin injection (1000 IU/kg) decreased circulatory S1P to 50&#xa0;% within 4&#xa0;h (p&#xa0;<&#xa0;0.0001). Continuous heparin application reduced the intima to media ratio by 74&#xa0;% compared to controls without heparin (p&#xa0;<&#xa0;0.001). CONCLUSIONS: Circulating S1P concentrations in patients with atherosclerosis are associated to different blood components before and after interventions. Reduced postoperative serum S1P levels in patients are most likely attributed to heparin treatment. The causalities between heparin treatment, reduced serum S1P and reduced intimal hyperplasia deserve further investigations.