Ceramides, composed of a sphingosine and a fatty acid, are bioactive lipid molecules involved in many key cellular pathways (e.g., apoptosis, oxidative stress and inflammation). There is much evidence on the relationship between ceramide species and cardiometabolic disease, especially in relationship with the onset and development of diabetes and acute and chronic coronary artery disease. This review reports available evidence on ceramide structure and generation, and discusses their role in cardiometabolic disease, as well as current translational chances and difficulties for ceramide application in the cardiometabolic clinical settings.

It is commonly believed that the inactivation of inflammation is mainly due to the decay or cessation of inducers. In reality, in connection with the development of atherosclerosis, spontaneous decay of inducers is not observed. It is now known that lipid mediators originating from polyunsaturated fatty acids (PUFAs), which are important constituents of all cell membranes, can act in the inflamed tissue and bring it to resolution. In fact, PUFAs, such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are precursors to both pro-inflammatory and anti-inflammatory compounds. In this review, we describe the lipid mediators of vascular inflammation and resolution, and their biochemical activity. In addition, we highlight data from the literature that often show a worsening of atherosclerotic disease in subjects deficient in lipid mediators of inflammation resolution, and we also report on the anti-proteasic and anti-thrombotic properties of these same lipid mediators. It should be noted that despite promising data observed in both animal and in vitro studies, contradictory clinical results have been observed for omega-3 PUFAs. Many further studies will be required in order to clarify the observed conflicts, although lifestyle habits such as smoking or other biochemical factors may often influence the normal synthesis of lipid mediators of inflammation resolution.

Background: Oxidative stress is crucial in the pathogenesis of atherosclerosis and acute myocardial infarction (AMI). Under the generic terms “oxidative stress” (OS), many biomarkers belonging to different pathways have been proposed. Aim: To compare the levels of recently proposed OS-related parameters in acute coronary syndromes (ACS) and stable coronary artery disease (CAD), to evaluate their effectiveness as additive risk or illness indicators of stable and acute ischemic events, and their response over time during the course of AMI. Methods: 76 ACS, 77 CAD patients, and 63 controls were enrolled in the study. Different OS-related biomarkers, including reactive oxygen metabolites (ROM), the total antioxidant capacity (OXY), nitrite/nitrate (final nitric oxide products, NO_x), and Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), were evaluated. Moreover, time response during AMI course (admission, and 6, 12, 18, 24, 36, and 48 hours after, T0-T6, respectively) and correlation with traditional cardiovascular (CV) risk factors (age, gender, hypertension, diabetes mellitus, dyslipidemia, smoking habit) were also assessed. Results: Over time, ROM progressively increased while OXY and NO_x decreased. Kinetics of LOX-1 during AMI shows that this biomarker boosts early during the acute event (T1 and T2) and then progressively decreases, being significantly lower from T0 to T6. Different OS-related biomarkers were differentially associated with CV risk factors and CAD or ACS presence. Conclusion: Differences in OS-related biomarkers (between groups, according to the response over time during AMI, and to the presence of CV risk factors) confirmed OS involvement in the transition from healthy status to stable CAD and ACS, although evidencing the heterogeneous nature of redox processes. In future, a multi-marker panel including different biomarkers and pathways of oxidative stress could be evaluated as an additive tool to be used in the CV prevention, diagnosis, patient stratification, and treatment.

Background: Ceramides, biologically active lipids correlated to oxidative stress and inflammation, have been associated with adverse outcomes in acute myocardial infarction (AMI). The purpose of this study was to assess the association between ceramides/ratios included in the CERT1 score and increased cardiovascular (CV) risk, inflammatory and left ventricular function parameters in AMI. Methods: high performance liquid chromatography-tandem mass spectrometry was used to identify Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) levels and their ratios to Cer(d18:1/24:0), in 123 AMI patients (FTGM coronary unit, Massa, Italy). Results: Cer(d18:1/16:0): higher in female patients (<0.05), in patients with dyslipidemia (<0.05), and it directly and significantly correlated with aging, brain natriuretic peptide-BNP, erythrocyte sedimentation rate-ESR and fibrinogen. Cer(d18:1/18:0): higher in females (<0.01) and patients with dyslipidemia (<0.01), and increased according to the number of CV risk factors (considering hypertension, dyslipidemia and diabetes). Moreover, it significantly correlated with BNP, troponin at admission, ESR, C reactive protein-CRP, and fibrinogen. Cer(d18:1/24:1): significantly correlated with aging, BNP, fibrinogen and neutrophils. Cer(d18:1/16:0)/Cer(d18:1/24:0): higher in female patients (1.7; ≤0.05), and in those with multivessel disease (<0.05). Moreover, it significantly correlated with aging, BNP, CRP, ESR, neutrophil-to-lymphocyte ratio-NRL, and fibrinogen. Cer(d18:1/18:0)/Cer(d18:1/24:0): higher in female patients (<0.001), and increased according to age. Moreover, it was higher in patients with lower left ventricular ejection fraction (1.7, <0.05), and in those with multivessel disease (0.13 ± 0.06 vs. 0.10 ± 0.05 µM, <0.05), and correlates with BNP, ESR, CRP, fibrinogen and neutrophils, platelets, NLR, and troponin at admission. Multiple regression analysis showed that Cer(d18:1/16:0)/Cer(d18:1/24:0) and Cer(d18:1/18:0)/Cer(d18:1/24:0) remained as independent determinants for WMSI after multivariate adjustment (Std coeff 0.17, T-value 1.9, ≤0.05; 0.21, 2.6, <0.05, respectively). Conclusion: Distinct ceramide species are associated with CV risk, inflammation and disease severity in AMI. Thus, a detailed analysis of ceramides may help to better understand CV pathobiology and suggest these new biomarkers as possible risk predictors and pharmacological targets in AMI patients.

Telomere shortening, chromosomal damage, and mitochondrial dysfunction are major initiators of cell aging and biomarkers of many diseases. However, the underlying correlations between nuclear and mitochondrial DNA alterations remain unclear. We investigated the relationship between telomere length (TL) and micronucleus (MN) and their association with mitochondrial DNA copy number (mtDNAcn) in peripheral blood mononuclear cells (PBMCs) in response to 100 μM and 200 μM of hydrogen peroxide (H₂O₂) at 44, 72, and 96 h. Significant TL shortening was observed after both doses of H₂O₂ and at all times (all p < 0.05). A concomitant increase in MN was found at 72 h (p < 0.01) and persisted at 96 h (p < 0.01). An increase in mtDNAcn (p = 0.04) at 200 µM of H₂O₂ was also found. In PBMCs treated with 200 µM H₂O₂, a significant inverse correlation was found between TL and MN (r = −0.76, p = 0.03), and mtDNA content was directly correlated with TL (r = 0.6, p = 0.04) and inversely related to MN (r = −0.78, p = 0.02). Telomere shortening is the main triggering mechanism of chromosomal damage in stimulated T lymphocytes under oxidative stress. The significant correlations between nuclear DNA damage and mtDNAcn support the notion of a telomere–mitochondria axis that might influence age-associated pathologies and be a target for the development of relevant anti-aging drugs.

The study aims are to evaluate the analytical performance and the clinical results of the chemiluminescent Access AccuTnI + 3 immunoassay for the determination of cardiac troponin I (cTnI) with DxI 800 and Access2 platforms and to compare the clinical results obtained with this method with those of three cTnI immunoassays, recently introduced in the European market. The limits of blank (LoB), detection (LoD), and quantitation (LoQ) at 20% CV and 10% CV were 4.5 ng/L and 10.9 ng/L, 17.1 and 30.4 ng/L, respectively. The results of STAT Architect high Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI third generation (Tosoh Bioscience), and Access AccuTnI + 3 (Beckman Coulter Diagnostics) showed very close correlations (R ranging from 0.901 to 0.994) in 122 samples of patients admitted to the emergency department. However, on average there was a difference up to 2.4-fold between the method measuring the highest (ADVIA method) and lowest cTnI values (AccuTnI + 3 method). The consensus mean values between methods ranged from 6.2% to 29.6% in 18 quality control samples distributed in an external quality control study (cTnI concentrations ranging from 29.3 ng/L to 1557.5 ng/L). In conclusion, the results of our analytical evaluation concerning the AccuTnI + 3 method, using the DxI platform, are well in agreement with those suggested by the manufacturer as well as those reported by some recent studies using the Access2 platform. Our results confirm that the AccuTnI + 3 method for the Access2 and DxI 800 platforms is a clinically usable method for cTnI measurement.