Abstract
There is a need for new biomarkers of atherosclerotic cardiovascular disease (ACVD), the main cause of death globally. Ceramides, a class of potent bioactive lipid mediators, have signalling roles in apoptosis, cellular stress and inflammation. Recent studies have highlighted circulating ceramides as novel biomarkers of coronary artery disease, type-2 diabetes and insulin resistance. Ceramides are highly regulated by enzymatic reactions throughout the body in terms of their activity and metabolism, including production, degradation and transport. The genetic studies that have been completed to date on the main ceramide species found in circulation are described, highlighting the importance of DNA variants in genes involved in ceramide biosynthesis as key influencers of heritable, circulating ceramide levels. We also review studies of disease associations with ceramides and discuss mechanistic insights deriving from recent genomic studies. The signalling activities of ceramides in vascular inflammation and apoptosis, associations between circulating ceramides and coronary artery disease risk, type-2 diabetes and insulin resistance, and the potential importance of ceramides with regard to ACVD risk factors, such as blood pressure, lipoproteins and lifestyle factors, are also discussed.
Highlights
There is a need for new biomarkers of atherosclerotic cardiovascular disease (ACVD), the main cause of death globally
This review describes the potential value of circulating ceramide species in ACVD-risk and discusses novel insights from recent phenotypic and genetic studies
The majority of circulating ceramides belong to the CER[NS] class of species containing a non-hydroxy fatty acid [N] attached to sphingosine [S]; for example, a ceramide with a 24-carbon non-hydroxy fatty acid and a 18-carbon sphingosine is denoted as CER[N(24)S(18)] (Fig. 1B)
Summary
Traditional biomarkers of atherosclerotic cardiovascular disease (ACVD), such as blood levels of lipoproteins, fail to identify all patients at high risk of cardiovascular events (reviewed in Ref. [1]). Traditional biomarkers of atherosclerotic cardiovascular disease (ACVD), such as blood levels of lipoproteins, fail to identify all patients at high risk of cardiovascular events Ceramides are a class of bioactive lipids which are present during vascular inflammation [2,3,4,5,6]. Their signalling properties mainly involve the regulation of apoptosis [7]. This review describes the potential value of circulating ceramide species in ACVD-risk and discusses novel insights from recent phenotypic and genetic studies. A number of in vitro ex periments supporting clinical findings have been published (e.g. Refs. [7,16,17]) but their detailed examination is outside the scope of this review
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