The role of sphingolipids in cardiovascular pathologies

Abstract

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.

Circulating Ceramide: A New Cardiometabolic Biomarker in Patients With Comorbid Acute Coronary Syndrome and Type 2 Diabetes Mellitus

“…The increase in ceramide content in LDL promotes the atherosclerotic process of the vascular wall (Li et al, 2014). Ceramides are involved in biological processes that may influence atherosclerosis and cardiovascular events, including oxidative stress apoptosis, endothelial dysfunction, inflammation, lipotoxicity, and insulin resistance (Alessenko et al, 2018). The inflammatory cytokines interferon-γ and IL-6 promote ceramide synthesis.…”

Sphingolipids in the Heart: From Cradle to Grave

“…As a result of chronic CAD, myocardial infarction (MI) and HF often occur. In contrast to much literature implicating ceramides as inducers of CVDs, pronounced cardiogenic and cardioprotective properties have been attributed to S1P ( 92 – 101 ).…”

Differences in plasma levels of long chain and very long chain ceramides between African Americans and whites: An observational study

“…Moreover, the authors showed that African Americans had less age-related increases in ceramides after controlling for potentially confounding variables including education, BMI and statin use. Notably, we ascertained the impact of race on plasma ceramide concentrations in subjects with and without metabolic disorders that have been previously shown to affect ceramides such as diabetes [29], hypercholesterolemia [3], and hypertension [15]. One possible explanation for this is the finding that sphingomyelin concentrations, are significantly higher in African Americans compared to whites [30].…”

“…African Americans have not equally benefited from population-wide cardiovascular disease (CVD) prevention programs and are still twice as likely to die from heart disease compared to non-Hispanic whites [1–3]. Significant disparities in age of onset and the prevalence of hypertension, diabetes, and obesity underscore a higher burden of CVD and coronary heart disease (CHD) in African Americans [4–7].…”