sphingosine-1-phosphate and Peripheral-Arterial-Disease

Cardiovascular diseases (CVDs) are the leading cause of death globally and the number of cardiovascular patients, which is estimated to be over 30 million in 2018, represent a challenging issue for the healthcare systems worldwide. Therefore, the identification of novel molecular targets to develop new treatments is an ongoing challenge for the scientific community. In this context, sphingolipids (SLs) have been progressively recognized as potent bioactive compounds that play crucial roles in the modulation of several key biological processes, such as proliferation, differentiation, and apoptosis. Furthermore, SLs involvement in cardiac physiology and pathophysiology attracted much attention, since these molecules could be crucial in the development of CVDs. Among SLs, ceramide and sphingosine-1-phosphate (S1P) represent the most studied bioactive lipid mediators, which are characterized by opposing activities in the regulation of the fate of cardiac cells. In particular, maintaining the balance of the so-called ceramide/S1P rheostat emerged as an important novel therapeutical target to counteract CVDs. Thus, this review aims at critically summarizing the current knowledge about the antithetic roles of ceramide and S1P in cardiomyocytes dysfunctions, highlighting how the modulation of their metabolism through specific molecules, such as myriocin and FTY720, could represent a novel and interesting therapeutic approach to improve the management of CVDs.

Topics: Aged; Animals; Ceramides; Cerebrovascular Disorders; Coronary Disease; Humans; Lysophospholipids; Mice; Peripheral Arterial Disease; Pulmonary Embolism; Rheumatic Heart Disease; Sphingolipids; Sphingosine; Venous Thrombosis

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.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Atherosclerosis; Blood Coagulation; Carotid Stenosis; Case-Control Studies; Cholesterol, HDL; Cohort Studies; Female; Humans; Lipoproteins, HDL; Lysophospholipids; Male; Middle Aged; Peripheral Arterial Disease; Prognosis; Regression Analysis; Risk Factors; ROC Curve; Signal Transduction; Sphingosine; Young Adult

Currently, the relationship between circulating lipids and abdominal aortic aneurysm (AAA) is unclear. We conducted a lipidomic analysis to identify serum lipids associated with AAA presence. Secondary analyses assessed the ability of models incorporating lipidomic features to improve stratification of patient groups with and without AAA beyond traditional risk factors.. Serum lipids were profiled via liquid chromatography tandem mass spectrometry analysis of serum from 161 patients with AAA and 168 controls with peripheral artery disease. Binary logistic regression was used to identify AAA-associated lipids. Classification models were created based on a combination of (1) traditional risk factors only or (2) lipidomic features and traditional risk factors. Model performance was assessed using receiver operator characteristic curves. Three diacylglycerols and 7 triacylglycerols were associated with AAA. Combining lipidomic features with traditional risk factors significantly improved stratification of AAA and peripheral artery disease groups when compared with traditional risk factors alone (mean area under the receiver operator characteristic curve [95% confidence interval], 0.760 [0.756-0.763] and 0.719 [0.716-0.723], respectively; P<0.05).. A group of linoleic acid containing triacylglycerols and diacylglycerols were significantly associated with AAA presence. Inclusion of lipidomic features in multivariate analyses significantly improved prediction of AAA presence when compared with traditional risk factors alone.

Topics: Aged; Aortic Aneurysm, Abdominal; Area Under Curve; Chromatography, High Pressure Liquid; Diglycerides; Female; Humans; Lipids; Logistic Models; Lysophospholipids; Male; Middle Aged; Odds Ratio; Peripheral Arterial Disease; Risk Factors; ROC Curve; Sphingosine; Tandem Mass Spectrometry; Triglycerides