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

Abstract

Background and ObjectivesAtherosclerotic 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 ResultsSerum 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.ConclusionsOur 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.

Sphingosine Kinases and Sphingosine 1-Phosphate Receptors: Signaling and Actions in the Cardiovascular System

“…In light of the evidence discussed above, it is important to consider that blood plasma and serum typically contains, in principle, high levels of S1P ( Murata et al, 2000 ; Deutschman et al, 2003 ). Importantly, changes in serum S1P may be a predictive marker for the presence and severity of cardiovascular disease, as in the case of obstructive coronary artery disease (CAD), atherosclerosis, myocardial infarction (MI) and HF in humans ( Deutschman et al, 2003 ; Sattler et al, 2010 ; Argraves et al, 2011 ; Cannavo et al, 2013b ; Egom et al, 2013 ; Soltau et al, 2016 ).…”

Determinants of Serum- and Plasma Sphingosine-1-Phosphate Concentrations in a Healthy Study Group

“…8,9 These properties of S1P gave rise to several preclinical studies testing for associations between circulatory S1P concentrations and clinical parameters in Dengue fever, 10,11 sepsis, 7,12,13 and atherosclerotic diseases. [14][15][16] In these studies, S1P has been measured in either serum or plasma whereby higher concentrations are generally seen in serum. This difference is attributed to platelets that release S1P during coagulation.…”

Sphingolipids in the Heart: From Cradle to Grave

“…As a result of chronic CAD, myocardial infarction (MI) and HF often occur. In contrast to much literature implicating ceramides as inducers of CVDs, pronounced cardiogenic and cardioprotective properties have been attributed to S1P (92)(93)(94)(95)(96)(97)(98)(99)(100)(101).…”