scholarly journals The role of sphingolipids in cardiovascular pathologies

2018 ◽  
Vol 64 (6) ◽  
pp. 487-495 ◽  
Author(s):  
A.V. Alessenko ◽  
A.T. Lebedev ◽  
I.N. Kurochkin
Keyword(s):  
Aliphatic Alcohol ◽  
Profile Analysis ◽  
Ischemia Reperfusion ◽  
Significant Risk ◽  
Density Lipoprotein ◽  
Industrialized Countries ◽  
Sphingosine 1 Phosphate ◽  
Cardiovascular Pathologies

Cardiovascular diseases (CVD) remain the leading cause of death in industrialized countries. One of the most significant risk factors for atherosclerosis is hypercholesterolemia. Its diagnostics is based on routine lipid profile analysis, including the determination of total cholesterol, low and high density lipoprotein cholesterol, and triglycerides. However in recent years, much attention has been paid to the crosstalk between the metabolic pathways of the cholesterol and sphingolipids biosynthesis. Sphingolipids are a group of lipids, containing a molecule of aliphatic alcohol sphingosine. These include sphingomyelins, cerebrosides, gangliosides and ceramides, sphingosines, and sphingosine-1-phosphate (S-1-P). It has been found that catabolism of sphingolipids is associated with catabolism of cholesterol. However, the exact mechanism of this interaction is still unknown. Particular attention as CVD inducer attracts ceramide (Cer). Lipoprotein aggregates isolated from atherosclerotic pluques are enriched with Cer. The level of Cer and sphingosine increases after ischemia reperfusion of the heart, in the infarction zone and in the blood, and also in hypertension. S-1-P exhibits pronounced cardioprotective properties. Its content sharply decreases with ischemia and myocardial infarction. S-1-P presents predominantly in HDL, and influences their multiple functions. Increased levels of Cer and sphingosine and decreased levels of S-1-P formed in the course of coronary heart disease can be an important factor in the development of atherosclerosis. It is proposed to use determination of sphingolipids in blood plasma as markers for early diagnosis of cardiac ischemia and for hypertension in humans. There are intensive studies aimed at correction of metabolism S-1-P. The most successful drugs are those that use S-1-P receptors as a targets, since all of its actions are receptor-mediated.

scholarly journals Endothelial Spns2 and ApoM Regulation of Vascular Tone and Hypertension Via Sphingosine‐1‐Phosphate

2021 ◽  
Author(s):  
Ilaria Del Gaudio ◽  
Luisa Rubinelli ◽  
Linda Sasset ◽  
Christian Wadsack ◽  
Timothy Hla ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Vascular Tone ◽  
Density Lipoprotein ◽  
No Production ◽  
Beneficial Effects ◽  
Increased Risk ◽  
Sphingosine 1 Phosphate

Background Most of the circulating sphingosine‐1‐phosphate (S1P) is bound to ApoM (apolipoprotein M) of high‐density lipoprotein (HDL) and mediates many beneficial effects of HDL on the vasculature via G protein–coupled S1P receptors. HDL‐bound S1P is decreased in atherosclerosis, myocardial infarction, and diabetes mellitus. In addition to being the target, the endothelium is a source of S1P, which is transported outside of the cells by Spinster‐2, contributing to circulating S1P as well as to local signaling. Mice lacking endothelial S1P receptor 1 are hypertensive, suggesting a vasculoprotective role of S1P signaling. This study investigates the role of endothelial‐derived S1P and ApoM‐bound S1P in regulating vascular tone and blood pressure. Methods and Results ApoM knockout (ApoM KO) mice and mice lacking endothelial Spinster‐2 (ECKO‐Spns2) were infused with angiotensin II for 28 days. Blood pressure, measured by telemetry and tail‐cuff, was significantly increased in both ECKO‐Spns2 and ApoM KO versus control mice, at baseline and following angiotensin II. Notably, ECKO‐Spns2 presented an impaired vasodilation to flow and blood pressure dipping, which is clinically associated with increased risk for cardiovascular events. In hypertension, both groups presented reduced flow‐mediated vasodilation and some degree of impairment in endothelial NO production, which was more evident in ECKO‐Spns2. Increased hypertension in ECKO‐Spns2 and ApoM KO mice correlated with worsened cardiac hypertrophy versus controls. Conclusions Our study identifies an important role for Spinster‐2 and ApoM‐HDL in blood pressure homeostasis via S1P‐NO signaling and dissects the pathophysiological impact of endothelial‐derived S1P and ApoM of HDL‐bound S1P in hypertension and cardiac hypertrophy.

scholarly journals Opposing Roles of S1P3 Receptors in Myocardial Function

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1770
Author(s):  
Dina Wafa ◽  
Nóra Koch ◽  
Janka Kovács ◽  
Margit Kerék ◽  
Richard L. Proia ◽  
...  
Keyword(s):  
Myocardial Function ◽  
Ischemia Reperfusion ◽  
Protective Action ◽  
Substantial Reduction ◽  
Cardiac Performance ◽  
Wild Type ◽  
Coronary Vasoconstriction ◽  
Coronary Syndrome ◽  
Sphingosine 1 Phosphate

Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator with diverse biological function mediated by S1P1–5 receptors. Whereas S1P was shown to protect the heart against ischemia/reperfusion (I/R) injury, other studies highlighted its vasoconstrictor effects. We aimed to separate the beneficial and potentially deleterious cardiac effects of S1P during I/R and identify the signaling pathways involved. Wild type (WT), S1P2-KO and S1P3-KO Langendorff-perfused murine hearts were exposed to intravascular S1P, I/R, or both. S1P induced a 45% decrease of coronary flow (CF) in WT-hearts. The presence of S1P-chaperon albumin did not modify this effect. CF reduction diminished in S1P3-KO but not in S1P2-KO hearts, indicating that in our model S1P3 mediates coronary vasoconstriction. In I/R experiments, S1P3 deficiency had no influence on postischemic CF but diminished functional recovery and increased infarct size, indicating a cardioprotective effect of S1P3. Preischemic S1P exposure resulted in a substantial reduction of postischemic CF and cardiac performance and increased the infarcted area. Although S1P3 deficiency increased postischemic CF, this failed to improve cardiac performance. These results indicate a dual role of S1P3 involving a direct protective action on the myocardium and a cardiosuppressive effect due to coronary vasoconstriction. In acute coronary syndrome when S1P may be released abundantly, intravascular and myocardial S1P production might have competing influences on myocardial function via activation of S1P3 receptors.

scholarly journals Beneficial Role of Mushroom in Recovering Complications of Hypercholesterolemia

2021 ◽  
Vol 4 (2) ◽  
pp. 1-14
Author(s):  
Swarup Kumar Kundu ◽  
Md. Abu Hadi Noor Ali Khan ◽  
Shonkor Kumar Das
Keyword(s):  
Portal Vein ◽  
Lipid Profile ◽  
Profile Analysis ◽  
Density Lipoprotein ◽  
Liver Weight ◽  
Histological Changes ◽  
Beneficial Role ◽  
Hypercholesterolemic Diet ◽  
Group B

Mushrooms are considered as a valuable source of important nutrients having hepatoprotective and anti-hyperlipidemic actions. Present experimental research was done to explore the beneficial role of mushroom on health in hypercholesterolemia. Total thirty Swiss albino mice were taken and randomly divided into three groups: control A, group B and group C. Each group consisted of ten mice. The control A group was fed with normal mice pellet and fresh water. Group B was fed with hypercholesterolemic diet and group C was supplied hypercholesterolemic diet with mushroom powder (500g/kg/mice body weight) for 60 days. After the experimental tenure, mice of each group were sacrificed ethically and the samples (liver and blood) were collected for gross, histological study and lipid profile analysis.  Increased liver weight, pale and hemorrhagic liver in gross observation along with some histological changes including dilation and congestion of central and portal vein, fat accumulation in hepatocyte and marked lymphocytic infiltration were found in group B, while mushroom supplementation recovered this gross and histological changes and reduced liver weight in group C. Just mild congestion and dilation was in the portal vein of group C. In lipid profile analysis, total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) level significantly reduced respectively by 10%, 38% and 17% in group C than group B. High density lipoprotein (HDL) level also significantly increased by 20% in group C compared to group B. Therefore, it can be concluded that mushrooms might have potentially beneficial actions in recovering of some complications in hypercholesterolemia.

Statistical interpretation of concentrations of magnesium, zinc, calcium, potassium, cholesterols, and creatine kinase isoenzymes in men at different stages of ischemic heart disease.

1989 ◽  
Vol 35 (5) ◽  
pp. 833-835 ◽  
Author(s):  
M Speich ◽  
J L Auget ◽  
P Arnaud
Keyword(s):  
Creatine Kinase ◽  
Interleukin 1 ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Hierarchical Cluster ◽  
Special Role ◽  
Statistical Interpretation ◽  
Total Creatine

Abstract We present a statistical interpretation of plasma (Pl) and (or) erythrocyte (Erc) concentrations of magnesium, zinc, calcium, potassium, and total high-density lipoprotein (HDL) cholesterol, as well as of the activity of total creatine kinase (CK) and its CK-MB isoenzyme, in 26 men with pre-infarction syndrome (PIS) and 34 men with acute myocardial infarction (MI). Discriminant analysis allowed overall comparison of both groups and determination of the most significant variables: CK and Pl-Zn. By non-hierarchical cluster analysis we defined three homogeneous subgroups among MI men, with CK, CK-MB, and Pl-Zn differing significantly between the groups. In PIS men, Pl-Zn was correlated with Pl-Ca, whereas in MI men Pl-Zn was correlated with Pl-Mg. Stepwise regression indicated that Pl-Zn was the most significant regressor of CK in PIS men and of CK-MB in MI men. All these statistical interpretations support a special role of Pl-Zn in diagnosis and perhaps prognosis. After MI, interleukin-1 release may possibly mediate observed hypozincemia via formation of a heart Zn-metallothionein.

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