The Role of Sphingolipids in Cardiovascular Pathologies

Cardiovascular diseases (CVD) remain the leading cause of death in industrialized countries. One of the most important risk factors for atherosclerosis is hypercholesterolemia; its diagnostics is mainly based on regular analysis of the lipid profile, 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 metabolic pathways of cholesterol and sphingolipid biosynthesis. Sphingolipids are a group of lipids that include a molecule of sphingosine aliphatic alcohol. These include sphingomyelins, cerebrosides, gangliosides, ceramides, sphingosines, and sphingosine-1-phosphate. It has been found that sphingolipid catabolism is associated with cholesterol catabolism. However, the exact mechanism of this interaction still remains unknown. Ceramide attracts particular attention as a CVD inducer. Aggregated lipoproteins isolated from atherosclerotic zones were found to be enriched with ceramides. Ceramide and sphingosine levels increase after ischemia/reperfusion of the heart, in the infarction area and in the blood, as well as in hypertension. Sphingosine-1-phosphate (S-1-P) exhibits pronounced cardioprotective properties. Its quantity sharply decreased during ischemia and myocardial infarction. S-1-P predominated in the structure of high-density lipoproteins (HDL), where it has a significant impact on their multiple functions. An increase in ceramide and sphingosine and a decrease in S-1-P levels during progression of coronary heart disease may be an important factor in the development of atherosclerosis. It is proposed to use determination of sphingolipid levels in the blood plasma as markers for early diagnostics of cardiac ischemia and in hypertension in humans. Recently, intensive studies have been undertaken to create drugs that can correct S-1-P metabolism. The most successful developments include agents targeted to the S-1-P receptor, which mediates all S-1-P effects. Chromatography-mass spectrometry is proposed as the main method for testing these lipids.