Plasma Ceramides as Prognostic Biomarkers and Their Arterial and Myocardial Tissue Correlates in Acute Myocardial Infarction

Abstract

Visual Abstract

Associations between specific plasma ceramides and severity of coronary-artery stenosis assessed by coronary angiography

“…Recently, de Carvalho et al showed myocardial upregulation of three ceramide-producing enzymes (i.e., ceramide synthase 6, serine palmitoyl transferase-2, and neutral sphingomyelinase) in a rodent model of acute myocardial infarction after LAD ligation. In this animal model, there was a net increase in production of long-chain ceramides [mainly Cer(d18:1/20:0), Cer(d18:1/22:0) and Cer(d18:1/24:0)] [24]. Collectively, these experimental findings may help also shed light on the results of our study that showed a strong association between increased levels of these plasma ceramides and severity of LAD stenosis.…”

Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia

“…Growing evidence suggests that the blood levels of ceramides are associated with the exacerbation of myocardial ischemic disease and its complications 7,40,49 . Studies on murine models revealed that pharmacological inhibition of the synthesis of ceramides prevents heart failure after myocardial ischemia, decreasing ventricular remodeling, fibrosis, and inflammatory infiltrate 8,43,50 . Similarly, the administration of an inhibitor of neutral SMases which hydrolyzes sphingomyelin to ceramide, thus impairing EV biogenesis, namely GW4869, reduced the increase of circulating inflammatory EV after MI in rats, resulting in the preservation of left ventricular ejection fraction 27 .…”

Why and how increased plasma ceramides predict future cardiovascular events?

“…transfer proteins may then further participate in exchange of ceramides between the circulating lipoproteins. Another source of circulating ceramides has been suggested to be an ischemic myocardial tissue, which thereby may contribute to an increase in the plasma levels of ceramides after an acute myocardial infarction [4]. This suggestion is supported by observations in rat models with myocardial ischemia showing that together with increased myocardial ceramide levels also the plasma levels of ceramides are increased [4,19,20].…”

“…Plasma ceramides (CER), a class of sphingolipid molecules, have been identified as markers of future cardiovascular (CV) events and measurement of certain ceramide species and their ratios in plasma samples can predict major acute CV events and CV mortality [1][2][3][4]. The data suggest that plasma ceramide levels may predict CV events more accurately than traditional risk biomarkers at least in patients with known atherosclerotic CV disease (CVD).…”

“…In accordance with data from earlier studies performed largely in Caucasian cohorts, high concentrations of ceramides containing fatty acids 16:0, 18:0, and 24:1 (CER16:0, CER18:0, and CER24:1) and low concentration of CER24:0 were associated with increased cardiovascular mortality. Based on the ratios of CER(16:0/24:0), CER(18:0/24:0), and CER(24:1/24:0), ceramide risk scores have been formulated and found to associate with an increased incidence of future cardiovascular events in earlier studies [1][2][3][4], and now also in the study by Li et al [5].…”