Ceramides in cardiovascular disease: emerging role as independent risk predictors and novel therapeutic targets

Abstract Ceramides are bioactive lipid mediators involved in apoptosis, inflammation, and fibrosis. This narrative review provides a concise overview of the emerging role of ceramides in cardiovascular disease with an emphasis on atherosclerotic vascular disease and heart failure, suggesting the potential use of ceramides in risk stratification and as putative therapeutic targets. Recent developments based on observational evidence and genetic associations, including Mendelian randomization studies in humans, are summarized and put into context with experimental evidence for the role of ceramides in human and animal models of disease. Emerging scores composed of ceramides and phosphatidylcholines that are based on the length and desaturation of the N-acyl chains are discussed in the light of novel data demonstrating age- and sex-specific differences. Also reviewed is the structural heterogeneity of the sphingoid bases, including non-conventional sphingolipids that are increasingly recognized for their importance in health and disease. Lastly, novel targets and potential modalities for tissue-specific transfer of drugs are discussed.