Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

Gosav, Evelina Maria; Petrov, Daniela; Jucan, Alina Ecaterina; Lǎcǎtusu, C.M.; Floria, Mariana; Tărniceriu, Claudia Cristina; Costea, Claudia Florida; Ciocoiu, Manuela; Rezuş, Ciprian

doi:10.3390/diagnostics11112053

Cited by 16 publications

(15 citation statements)

References 157 publications

(188 reference statements)

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“…In this context, additional therapies directed towards the inhibition of ceramide pathways (e.g., myriocin-inhibitor of serine palmitoyl-CoA transferase, an enzyme involved in up-regulation in de novo synthesis of ceramide), ceramide inhibitors (e.g., Fumonisin B1, fungin FTY720, etc. ), as well as inhibition of the downstream inflammatory pathway (e.g., methotrexate, which targets CERS6) are under study [ 66 , 67 ].…”

Section: Ceramides and Cardiometabolic Riskmentioning

confidence: 99%

Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease

Gaggini

Ndreu

Michelucci

et al. 2022

IJMS

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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.

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Section: Ceramides and Cardiometabolic Riskmentioning

confidence: 99%

Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease

Gaggini

Ndreu

Michelucci

et al. 2022

IJMS

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“…However, ceramides may retain even better predictivity of residual risk over traditional lipids, thus identifying high-risk patients also among those with low LDL-C, as evidenced in coronary artery disease patients [ 4 , 19 ]. This fact is important, as being ceramides modifiable by diet and exercise as well as by drugs (e.g., small molecule inhibitors of key enzymes, anti-inflammatory agents), it is therefore plausible that ceramide evaluation in the clinical setting may be relevant, especially if antioxidants/anti-inflammatory trials will give positive results [ 28 , 29 , 30 ]. Possible underlying mechanisms by which specific plasma ceramides might contribute to the pathophysiology of atherosclerosis are not fully cleared, although many data suggest that ceramide circulating changes might be a reflex of cardiovascular inflammation.…”

Section: Discussionmentioning

confidence: 99%

Ceramides and Cardiovascular Risk Factors, Inflammatory Parameters and Left Ventricular Function in AMI Patients

et al. 2022

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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 (<0.05), and in patients with higher wall motion score index-WMSI (>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 (<35%, ≤0.01), higher WMSI (>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.

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“…At 24 hpi where most T. canis larvae are present in the liver ( Schnieder et al., 2011 ), the liver appears to partly regain homeostasis with only 64 lipid species with differential abundance and 2 altered lipid subclasses (Cer and TG). Ceramides (Cer) play roles in signal transduction in vital processes, such as apoptosis and cell differentiation ( Takabe et al., 2008 ; Tanase et al., 2021 ). Cer was upregulated 1.25 times and 1.26 times, including one upregulated and five upregulated Cer lipid species at 12 and 24 hpi, respectively.…”

Section: Discussionmentioning

confidence: 99%

Lipidomic changes in the liver of beagle dogs associated with Toxocara canis infection

Zou

Elsheikha

et al. 2022

Front. Cell. Infect. Microbiol.

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A global lipidomic analysis using liquid chromatography–tandem mass spectrometry was performed on the liver of beagle dogs infected with Toxocara canis to profile hepatic lipid species at 12 h post-infection (hpi), 24 hpi, and 36 days post-infection (dpi). This analysis identified six categories and 42 subclasses of lipids, including 173, 64, and 116 differentially abundant lipid species at 12 hpi, 24 hpi, and 36 dpi, respectively. Many of the identified lysophospholipids, such as lysophosphatidylglycerol, lysophosphatidylserine, and lysophosphatidylcholine, may contribute to the migration and development of T. canis during the early infection stage. Pathway analysis revealed significant alterations of several immune-inflammatory pathways, such as the B-cell receptor signaling pathway, the NF-kappa B signaling pathway, and the C-type lectin receptor signaling pathway at 12 and 24 hpi. These findings demonstrate the value of lipidomic profiling in revealing the extent of changes in the composition and abundance of hepatic lipidome caused by T. canis infection and their relevance to the pathophysiology of toxocariasis in beagle dogs.

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Involvement of Ceramides in Non-Alcoholic Fatty Liver Disease (NAFLD) Atherosclerosis (ATS) Development: Mechanisms and Therapeutic Targets

Cited by 16 publications

References 157 publications

Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease

Ceramides as Mediators of Oxidative Stress and Inflammation in Cardiometabolic Disease

Ceramides and Cardiovascular Risk Factors, Inflammatory Parameters and Left Ventricular Function in AMI Patients

Lipidomic changes in the liver of beagle dogs associated with Toxocara canis infection

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