sphingosine-1-phosphate and Acute-Coronary-Syndrome

Sphingolipids have been recently elucidated to be not only mere components of the plasma membrane but also bioactive mediators which can induce various biological responses. Among these lipids, sphingomyelin(SM) and sphingosine 1-phosphate (Sph-1-P) are proposed to be involved in the pathogenesis of atherosclerosis: SM is abundant in atherosclerotic lesions and Sph-1-P is bound to HDL and attributes to the anti-atherosclerotic properties of HDL at least partly. Therefore, Sph-1-P and SM can be useful biomarkers for atherosclerotic disorders. However, at present, the measurement of Sph-1-P and SM levels has not been brought into clinical practice, yet. The main obstacle is the difficulty in measuring these sphingolipids precisely, rapidly, and conveniently. Recently, we have developed new methods for measuring Sph-1-P (HPLC method) and SM (enzymatic method). These methods are easy to be introduced into clinical laboratory testing because they do not need any special techniques and equipment. With this method for SM, we have demonstrated that the SM concentration was significantly higher in subjects with acute coronary syndrome. In this paper, we reviewed the possibility of sphingolipids as biomarkers for atherosclerotic disorders.

Topics: Acute Coronary Syndrome; Atherosclerosis; Biomarkers; Humans; Lysophospholipids; Sex Characteristics; Sphingolipids; Sphingosine

Complex signal-transduction cascades are known to be involved in regulating cardiomyocyte function, death and survival during acute cardiac ischemia-reperfusion process, but detailed survival signalling pathways are not clear. This review presents and discusses the recent findings bearing upon the evidence on the cardioprotective effect of sphingosine-1-phosphate (S1P) and bradykinin in acute cardiac ischemia-reperfusion and underlying signalling mechanisms, particularly, through activation of P21 activated kinase.

Topics: Acute Coronary Syndrome; Animals; Bradykinin; Humans; Lysophospholipids; p21-Activated Kinases; Reperfusion Injury; Signal Transduction; Sphingosine

Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that the atheroprotective role of HDL lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been investigated comprehensively.. We conducted a case-control study nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial in which participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (N=167) were individually matched (1:2) to control patients by sex, age, intervention group, body mass index, and follow-up time. We investigated 2 individual manifestations (myocardial infarction, unstable angina) as secondary outcomes. We measured the following functional characteristics: HDL cholesterol concentration (in plasma); cholesterol efflux capacity; antioxidant ability, measured by the HDL oxidative-inflammatory index; phospholipase A2 activity; and sphingosine-1-phosphate, apolipoproteins A-I and A-IV, serum amyloid A, and complement 3 protein (in apolipoprotein B-depleted plasma). We used conditional logistic regression models adjusted for HDL cholesterol levels and cardiovascular risk factors to estimate odds ratios (ORs) between 1-SD increments in HDL functional characteristics and clinical outcomes.. Low values of cholesterol efflux capacity (OR. Low cholesterol efflux capacity values, pro-oxidant/proinflammatory HDL particles, and low HDL levels of sphingosine-1-phosphate and apolipoprotein A-I were associated with increased odds of acute coronary syndrome and its manifestations in individuals at high cardiovascular risk.. URL: https://www.controlled-trials.com/ISRCTN35739639. Unique identifier: ISRCTN35739639.

Topics: Acute Coronary Syndrome; Aged; Apolipoprotein A-I; Case-Control Studies; Diet, Mediterranean; Female; Follow-Up Studies; Humans; Lipoproteins, HDL; Lysophospholipids; Male; Middle Aged; Sphingosine

Sphingosine 1-phosphate (S1P) has been suggested to be a positive regulator of plasminogen activator inhibitor 1 (PAI-1) in adipocytes, while some studies are not consistent with this prothrombotic property of S1P. Since S1P is bound to apolipoprotein M (apoM) on HDL or to albumin in plasma, we compared the properties of these two forms on the PAI-1 induction.. We investigated the associations of S1P, apoM, and PAI-1 concentrations in the plasma of normal coronary artery (NCA), stable angina pectoris (SAP), and acute coronary syndrome (ACS) subjects (n=32, 71, and 38, respectively). Then, we compared the effects of S1P with various vehicles on the PAI-1 expression in 3T3L1 adipocytes. We also investigated the modulation of the PAI-1 levels in mice infected with adenovirus coding apoM.. Among ACS subjects, the PAI-1 level was positively correlated with the S1P level, but not the apoM level. In adipocytes, S1P bound to an apoM-rich vehicle induced PAI-1 expression to a lesser extent than the control vehicle, while S1P bound to an apoM-depleted vehicle induced PAI-1 expression to a greater extent than the control vehicle in 3T3L1 adipocytes. Additionally, apoM overexpression in mice failed to modulate the plasma PAI-1 level and the adipose PAI-1 expression level. S1P bound to albumin increased PAI-1 expression through the S1P receptor 2-Rho/ROCK-NFκB pathway.. S1P bound to albumin, but not to apoM, induces PAI-1 expression in adipocytes, indicating that S1P can exert different properties on the pathogenesis of vascular diseases, depending on its vehicle.

Topics: 3T3-L1 Cells; Acute Coronary Syndrome; Adipocytes; Angina, Stable; Animals; Apolipoproteins M; Human Umbilical Vein Endothelial Cells; Humans; Lipoproteins, HDL; Lysophospholipids; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; NF-kappa B; Plasminogen Activator Inhibitor 1; Platelet Activation; Protein Binding; Receptors, Lysosphingolipid; Recombinant Proteins; Serpin E2; Serum Albumin, Human; Signal Transduction; Sphingosine; Sphingosine-1-Phosphate Receptors

Low high-density lipoprotein (HDL) cholesterol and loss of atheroprotective functions of HDL are associated with coronary artery disease (CAD). Here, we investigated the associations of HDL phospholipids with acute and stable CAD as well as with the anti-apoptotic activity of HDL.. 49 species of phosphatidylcholines (PCs), lysophosphatidylcholines and sphingomyelins (SMs) as well as three species of sphingosine-1-phosphate (S1P) were quantified by liquid chromatography - mass spectrometry in HDL isolated from 22 healthy subjects as well as 23 and 22 patients with stable CAD and acute coronary syndrome (ACS), respectively. Native HDL and artificially reconstituted HDL (rHDL) were tested for their capacity to inhibit apoptosis of endothelial cells (ECs) induced by serum deprivation.. HDL of CAD or ACS patients differed from HDL of healthy controls by the content in nine of the 52 quantified phospholipid species as well as reduced anti-apoptotic activity. The capacity of HDL to inhibit EC apoptosis correlated significantly with five of eleven odd-chain PC's (= plasmalogens), two S1P's, SM42:2, PC34:2, and PC32:0. An orthogonal partial least square - discriminant analysis revealed independent associations of stable CAD with HDL-associated PC34:2, PC33:3 and PC35:2 as well as anti-apoptotic activity of HDL and of ACS with HDL-associated PC33:3, PC35:2, SM42:1, PC34:2 and PC36:2. rHDL reconstituted with apoA-I, PC34:1, and PC35:2 inhibited apoptosis of EC's more effectively than rHDL containing only apoA-I and PC34:1.. The inverse association of HDL-plasmalogen levels with both stable and acute CAD may reflect direct anti-apoptotic effects of plasmologens on ECs.

Topics: Acute Coronary Syndrome; Adult; Aged; Apolipoprotein A-I; Apoptosis; Case-Control Studies; Chromatography, Liquid; Coronary Artery Disease; Discriminant Analysis; Endothelial Cells; Female; Humans; Least-Squares Analysis; Lipids; Lipoproteins, HDL; Lysophosphatidylcholines; Lysophospholipids; Male; Mass Spectrometry; Middle Aged; Phosphatidylcholines; Plasmalogens; Sphingomyelins; Sphingosine