Serum-Sphingosine-1-Phosphate Concentrations Are Inversely Associated with Atherosclerotic Diseases in Humans.

Atherosclerotic changes of arteries are the leading cause for deaths in cardiovascular disease and greatly impair patient's quality of life. Sphingosine-1-phosphate (S1P) is a signaling sphingolipid that regulates potentially pro-as well as anti-atherogenic processes. Here, we investigate whether serum-S1P concentrations are associated with peripheral artery disease (PAD) and carotid stenosis (CS).Serum was sampled from blood donors (controls, N = 174) and from atherosclerotic patients (N = 132) who presented to the hospital with either clinically relevant PAD (N = 102) or CS (N = 30). From all subjects, serum-S1P was measured by mass spectrometry and blood parameters were determined by routine laboratory assays. When compared to controls, atherosclerotic patients before invasive treatment to restore blood flow showed significantly lower serum-S1P levels. This difference cannot be explained by risk factors for atherosclerosis (old age, male gender, hypertension, hypercholesteremia, obesity, diabetes or smoking) or comorbidities (Chronic obstructive pulmonary disease, kidney insufficiency or arrhythmia). Receiver operating characteristic curves suggest that S1P has more power to indicate atherosclerosis (PAD and CS) than high density lipoprotein-cholesterol (HDL-C). In 35 patients, serum-S1P was measured again between one and six months after treatment. In this group, serum-S1P concentrations rose after treatment independent of whether patients had PAD or CS, or whether they underwent open or endovascular surgery. Post-treatment S1P levels were highly associated to platelet numbers measured pre-treatment.Our study shows that PAD and CS in humans is associated with decreased serum-S1P concentrations and that S1P may possess higher accuracy to indicate these diseases than HDL-C

Association of serum-S1P levels with risk factors for atherosclerosis and comorbidities in atherosclerotic patients.

<p>Association of serum-S1P levels with risk factors for atherosclerosis and comorbidities in atherosclerotic patients.</p

Association of blood parameters with serum-S1P in controls and atherosclerotic patients pre-treatment.

<p>Association of blood parameters with serum-S1P in controls and atherosclerotic patients pre-treatment.</p

Multivariate regression analysis with backward elimination.

<p>Multivariate regression analysis with backward elimination.</p

Characteristics of the recovery group.

<p>Characteristics of the recovery group.</p

S1P may have more power to indicate atherosclerosis (PAD and CS) than HDL-C.

<p>Receiver operating characteristic (ROC) curves were generated for S1P and HDL-C measured in controls (N = 174) and atherosclerotic patients (N = 132). The dotted line represents the line of identity. *the AUC for S1P and HDL-C are significantly different (P <0.05)</p

Serum-S1P levels rise after treatment.

<p>Serum-S1P was measured in 35 patients between one and six months after treatment (recovery cohort). <b>A</b>; serum S1P in the recovery cohort (N = 35) was compared before and after treatment to restore blood flow. Data are presented as median with maximum, minimum and 3^rd and 1^st quartiles. Statistical analysis was performed by two-tailed, paired T-test. <b>B</b>; the recovery cohort was classified into two groups at a time, CS patients (N = 8) and PAD patients (N = 27) or as to the form of treatment (open (N = 28) or endovascular (N = 7)). The serum-S1P concentrations (mean +/- SD) before and after treatment are shown for each group. Statistical analysis was performed by two-tailed T-test. *P<0.05; n.s. = non-significant. <b>C</b>; using data obtained from the recovery cohort, a regression analysis was performed for platelet numbers pre-treatment and serum-S1P in recovery (r = Spearman correlation coefficient).</p

Serum-S1P concentrations in healthy controls and atherosclerotic patients.

<p>Serum-S1P was measured in 174 blood donors (controls, Co) and 132 atherosclerotic patients (PAD + CS), 102 with primary PAD and 30 with primary CS. <b>A</b>; frequency histograms (percent of subjects vs. serum-S1P) are shown for controls (grey bars) and atherosclerotic patients (black bars). <b>B</b>; data are presented as median with maximum, minimum and 3^rd and 1^st quartiles. Statistical analysis was performed by the non-parametric Kruskal-Wallis test with correction for multiple comparisons. **Indicates significance of difference to controls (P<0.001). <b>C</b>; controls and atherosclerotic patients were divided into two groups each to yield one group each with the same median age of 60 years. Four groups with the following median age were formed: Controls (36 years, N = 105 and 60 years, N = 69) and patients (75 years, N = 79 and 60 years, N = 53). Serum-S1P for each group was compared to all other groups using the non-parametric Kruskal-Wallis test with correction for multiple comparisons. ** P<0.001, n.s. = non-significant (P>0.05).</p