Plasma Ceramides

Abstract

Objective- Ceramides are sphingolipids involved with cellular signaling. Synthesis of ceramides occurs in all tissues. Ceramides accumulate within tissues and the blood plasma during metabolic dysfunction, dyslipidemia, and inflammation. Elevations of ceramides are predictive of cardiovascular mortality. We sought to verify the utility of plasma concentrations of 4 ceramides: N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)], and N-lignoceroyl-sphingosine [Cer(24:0)] in predicting major adverse cardiovascular events in a diverse patient population referred for coronary angiography. Approach and Results- Plasma ceramides were measured in 495 participants before nonurgent coronary angiography. Coronary artery disease, defined as >50% stenosis in ≥1 coronary artery, was identified 265 (54%) cases. Ceramides were not significantly associated with coronary artery disease. Patients were followed for a combined primary end point of myocardial infarction, percutaneous intervention, coronary artery bypass, stroke, or death within 4 years. Ceramides were significantly predictive of outcomes after adjusting for age, sex, body mass index, hypertension, smoking, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, triglycerides, serum glucose, and family history of coronary artery disease. The fully adjusted per SD hazard ratios (95% confidence interval) were 1.50 (1.16-1.93) for Cer(16:0), 1.42 (1.11-1.83) for Cer(18:0), 1.43 (1.08-1.89) for Cer(24:1), and 1.58 (1.22-2.04) for the ceramide risk score. Conclusions- Elevated plasma concentrations of ceramides are independently associated with major adverse cardiovascular events in patients with and without coronary artery disease.

Metabolomic Profiles Associated with BMI, Waist Circumference, and Diabetes and Inflammation Biomarkers in Women

“…Thus, most studies have focused on the more prevalent SMs and ceramides containing the double bond in the sphingoid base backbone. In fact, ceramides with C16:0, C18:0, C20:0, and C24:1 acyl chains are currently the subject of considerable interest because they have been linked to insulin resistance (26) and risk of cardiovascular disease and mortality (40). While our association between dihydro-SM and CRP is novel, the association with c-peptide is consistent with findings for other sphingolipids and suggests that the dihydrosphingolipids may affect insulin secretion and metabolic health as well.…”

Circulating ceramide ratios and risk of vascular brain aging and dementia

“…Recent cardiovascular studies have consistently shown an increased risk of adverse vascular events and mortality in individuals with increased ratios of long-chain to very long-chain ceramides in plasma. 5,17,[31][32][33] In a murine model of ceramide synthase 2 haploinsufficiency, a reduction in levels of very long-chain (C22:0 and C24:0) ceramides and a compensatory increase in levels of longchain ceramides (C16:0) was noted, resulting in an increased susceptibility to insulin resistance and hepatocyte apoptosis. 30 Given the role of ceramides in pancreatic b-cell dysfunction, insulin resistance and vascular reactivity, 34 increased cardiometabolic risk could potentially mediate the association with dementia.…”

Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer

“…Most patients (n = 24) had no evidence of lymph node metastases. 34.1%, and 13.6% of cases at the time of diagnosis, respectively. In the vast majority of patients (95.4%), the depth of tumors was T2 and T3, i.e., 34.0%, and 61.4% of all cases, respectively.…”