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Published on: October 25, 2024
[Participation of Sphingolipids in the Pathogenesis of Atherosclerosis]
A V Alessenko1, D A Zateyshchikov2, A Т Lebedev3
1N.M. Emanuel Institute of Biochemical Physics.
Insights
Sphingolipids, like ceramides and sphingosine-1-phosphate (S-1-P), are crucial in cardiovascular disease development. Monitoring their levels may aid early diagnosis of heart issues and hypertension.
Area of Science:
- Biochemistry
- Cardiology
- Metabolomics
Background:
- Lipid metabolism disorders are primary risk factors for cardiovascular diseases (CVD).
- Sphingolipids, including ceramides and sphingosine-1-phosphate (S-1-P), intersect with cholesterol biosynthesis and impact cellular apoptosis.
- Elevated ceramides and reduced S-1-P are implicated in cardiovascular pathologies like atherosclerosis and hypertension.
Purpose of the Study:
- To investigate the role of sphingolipids in cardiovascular disease pathogenesis.
- To explore the potential of sphingolipid levels as biomarkers for early diagnosis of cardiac ischemia and hypertension.
Main Methods:
- Analysis of lipid metabolism pathways, focusing on cholesterol and sphingolipid biosynthesis.
- Measurement of ceramide, sphingosine, and S-1-P levels in biological samples.
- Chromatography-mass spectrometry proposed for sphingolipid quantification.
Main Results:
- Ceramides are enriched in atherosclerotic lesions and increase during cardiac ischemia/reperfusion and in hypertension.
- S-1-P levels decrease significantly during ischemia and myocardial infarction, despite its cardioprotective role.
- S-1-P is a key component of high-density lipoproteins (HDL), influencing their function.
Conclusions:
- Altered sphingolipid metabolism, specifically increased ceramides and decreased S-1-P, contributes to atherosclerosis development.
- Measuring sphingolipid levels in blood plasma shows promise for early diagnosis of cardiac ischemia and arterial hypertension.
- Targeting S-1-P receptors represents a potential therapeutic strategy for cardiovascular diseases.
Abstract:
Lipid metabolism disorders are the most significant risk factor of development of cardiovascular diseases (CVD). In the process of diagnosing ischemic heart disease and other cardiovascular pathologies, levels of total cholesterol, low- and high- density lipoprotein cholesterol, triglycerides are determined. However, in recent years, close attention has been paid to the intersection of the metabolic pathways of the biosynthesis of cholesterol and sphingolipids. Sphingolipids - a group of lipids, which include a molecule of aliphatic alcohol sphingosine. This group includes sphingomyelins, cerebrosides, gangliosides and ceramides, sphingosines and sphingosine-1-phosphate (S-1-P). Ceramides and sphingosines have pro-apoptotic properties, and S-1-P protects cells from apoptosis. Particular attention as inducer CVD attracts ceramide. It has been established that aggregated lipoproteins isolated from atherosclerotic zones are enriched with ceramides. The level of ceramide and sphingosine increases with ischemia/reperfusion of the heart, in the infarction zone and in the blood, and also in hypertensive disease. S-1-P has a pronounced cardioprotective properties. Its content sharply decreases with ischemia and myocardial infarction. S-1-P performs a special function in the structure of high-density lipoproteins (HDL), being one of the main lipid components of these lipoproteins, which determines their multiple functions. Recently, work has been underway to create drugs that can correct the metabolism of S-1-P. The most successful drugs are those that use the S-1-P receptor as a target, since all of its actions are carried out through receptors. Increasing ceramide and sphingosine and reducing blood plasma level of S-1-P can be an important factor in the development of atherosclerosis. It is proposed to use the determination of the level of sphingolipids in blood plasma for early diagnosis of cardiac ischemia and in arterial hypertension. Chromatography-mass spectrometry has been suggested as the main method for testing these lipids.
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