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

TY - JOUR

T1 - Serum-Sphingosine-1-Phosphate Concentrations Are Inversely Associated with Atherosclerotic Diseases in Humans

AU - Soltau, Irina

AU - Mudersbach, Eileen

AU - Geissen, Markus

AU - Schwedhelm, Edzard

AU - Winkler, Martin S

AU - Geffken, Maria

AU - Peine, Sven

AU - Schoen, Gerhard

AU - Debus, E Sebastian

AU - Larena-Avellaneda, Axel

AU - Daum, Guenter

PY - 2016

Y1 - 2016

N2 - BACKGROUND AND OBJECTIVES: 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).METHODS AND RESULTS: 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.CONCLUSIONS: 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.

AB - BACKGROUND AND OBJECTIVES: 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).METHODS AND RESULTS: 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.CONCLUSIONS: 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.

U2 - 10.1371/journal.pone.0168302

DO - 10.1371/journal.pone.0168302

M3 - SCORING: Journal article

C2 - 27973607

VL - 11

SP - e0168302

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 12

ER -