Dataset Information

Analysis of circulating ceramides and hexosylceramides in patients with coronary artery disease and type II diabetes mellitus.

ABSTRACT:

Background

Cardiovascular disease (CVD) remains the leading cause of death worldwide. The main driving force behind this association is coronary artery disease (CAD), the manifestation of atherosclerosis in the coronary circulation. Cornerstones in the development of CAD are pathologies in lipid metabolism. In recent years, ongoing research has identified ceramides, a subclass of sphingolipids to be mediators of CVD. The aim of this study is to investigate the influence of type II diabetes mellitus (DM) on circulating ceramides and hexosylceramides (HexCers) in CAD patients.

Methods

24 patients aged 40-90 years with CAD confirmed by angiography were included into a pilot study. Patients with DM were identified by analysis of discharge letters or other medical documents available at the study center. During coronary angiography, arterial blood samples were collected and quantification of sphingolipids in patient serum was performed by mass spectrometry.

Results

Statistical analysis showed nine significantly different HexCers in CAD patients with DM compared to patients without DM. Among the nine significantly regulated HexCers, we identified seven d18:1 HexCers. This group contributes to the fourth most abundant subgroup of total ceramides and HexCers in this dataset. HexCer-d18:1-23:1(2-OH) showed the strongest downregulation in the patient group with DM.

Conclusion

This study suggests that levels of circulating HexCers are downregulated in patients with CAD and concomitant DM compared to patients without DM. Further research is needed to investigate the underlying mechanisms and the suitability of HexCers as possible mediators and/or prognostic markers in CAD.

SUBMITTER: Dusing P

PROVIDER: S-EPMC10498560 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Analysis of circulating ceramides and hexosylceramides in patients with coronary artery disease and type II diabetes mellitus.

Düsing Philip P Heinrich Nadine N NN Al-Kassou Baravan B Gutbrod Katharina K Dörmann Peter P Nickenig Georg G Jansen Felix F Zietzer Andreas A

BMC cardiovascular disorders 20230912 1

<h4>Background</h4>Cardiovascular disease (CVD) remains the leading cause of death worldwide. The main driving force behind this association is coronary artery disease (CAD), the manifestation of atherosclerosis in the coronary circulation. Cornerstones in the development of CAD are pathologies in lipid metabolism. In recent years, ongoing research has identified ceramides, a subclass of sphingolipids to be mediators of CVD. The aim of this study is to investigate the influence of type II diabet ...[more]

PMID: 37700226

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Project description:BackgroundCoronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). Some studies reported the ceramide species are associated with the ACS and major adverse cardia and cerebrovascular events (MACE). However, few studies investigated the association between plasma ceramide levels and the severity of stenosis, together with the onset of diseases. This aim of the present study was to investigate the association betweencertain ceramide species, coronary artery stenosis and acute coronary syndrome.MethodsFive hundred fifty-three patients with definite or suspected CAD were recruited and received angiography. Subjects were assigned into 4 groups according to the severity of coronary artery stenosis. The measurements of 4 plasma ceramide species, namely, Cer (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), Cer (d18:1/24:0) were carried out by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the ratio of Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) to Cer (18:1/24:0), respectively, were calculated as index to evaluate the association between plasma ceramides levels and coronary artery stenosis. Multiple logistic regression analysis was used to establish the prognostic model for the prediction of ACS risk.ResultsAfter the adjustment by multiple clinical risk factors including age, gender, pre-existing myocardial/cerebral infarction, hemoglobin A1c% (HbA1c%), smoking and the diagnosis during index hospitalization, multiple logistic regression analysis showed that the high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c%, unstable angina (UAP) and acute myocardial infarction (AMI) diagnosis (compared with atherosclerosis) during index hospitalization were associated with more severe coronary artery stenosis. Furthermore, the prognostic model was established after adjustment of risk factors and the area under curve (AUC) of receiver operating characteristics (ROC) for the prognostic model was 0.732 and 95% CI was 0.642-0.822.ConclusionThe severity of coronary artery stenosis is associated with high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c% and AMI. Although the reported prognostic model showed a good discrimination, further investigation on long term MACE is needed to evaluate the role of ceramide for the prediction of MACE risk.

Project description:BackgroundCoronary artery disease (CAD) is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The purpose of the present study was to discriminate the Indian CAD patients with or without T2DM by using multiple pathophysiological biomarkers.MethodsUsing sensitive multiplex protein assays, we assessed 46 protein markers including cytokines/chemokines, metabolic hormones, adipokines and apolipoproteins for evaluating different pathophysiological conditions of control, T2DM, CAD and T2DM with CAD patients (T2DM_CAD). Network analysis was performed to create protein-protein interaction networks by using significantly (p < 0.05) altered protein markers in each disease using STRING 10.5 database. We used two supervised analysis methods i.e., between class analysis (BCA) and principal component analysis (PCA) to reveals distinct biomarkers profiles. Further, random forest classification (RF) was used to classify the diseases by the panel of markers.ResultsOur two supervised analysis methods BCA and PCA revealed a distinct biomarker profiles and high degree of variability in the marker profiles for T2DM_CAD and CAD. Thereafter, the present study identified multiple potential biomarkers to differentiate T2DM, CAD, and T2DM_CAD patients based on their relative abundance in serum. RF classified T2DM based on the abundance patterns of nine markers i.e., IL-1β, GM-CSF, glucagon, PAI-I, rantes, IP-10, resistin, GIP and Apo-B; CAD by 14 markers i.e., resistin, PDGF-BB, PAI-1, lipocalin-2, leptin, IL-13, eotaxin, GM-CSF, Apo-E, ghrelin, adipsin, GIP, Apo-CII and IP-10; and T2DM _CAD by 12 markers i.e., insulin, resistin, PAI-1, adiponectin, lipocalin-2, GM-CSF, adipsin, leptin, Apo-AII, rantes, IL-6 and ghrelin with respect to the control subjects. Using network analysis, we have identified several cellular network proteins like PTPN1, AKT1, INSR, LEPR, IRS1, IRS2, IL1R2, IL6R, PCSK9 and MYD88, which are responsible for regulating inflammation, insulin resistance, and atherosclerosis.ConclusionWe have identified three distinct sets of serum markers for diabetes, CAD and diabetes associated with CAD in Indian patients using nonparametric-based machine learning approach. These multiple marker classifiers may be useful for monitoring progression from a healthy person to T2DM and T2DM to T2DM_CAD. However, these findings need to be further confirmed in the future studies with large number of samples.

Project description:BACKGROUND:Little is known about whether mitochondria 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of mitochondrial DNA (mtDNA) oxidative damage, contributes to the development of coronary artery disease (CAD) in diabetic patients. Here, we explored the associations of mtDNA 8-OHdG in leukocytes with obstructive CAD, coronary stenosis severity, cardiovascular biomarkers, and 1-year adverse outcomes after coronary revascularization in patients with type 2 diabetes mellitus (T2DM). METHODS:In a total of 1920 consecutive patients with T2DM who underwent coronary angiography due to symptoms of angina or angina equivalents, the presence of obstructive CAD, the number of diseased vessels with ≥ 50% stenosis, and modified Gensini score were cross-sectionally evaluated; the level of mtDNA 8-OHdG was quantified by quantitative PCR. Then, 701 of 1920 diabetic patients who further received coronary revascularization completed 1-year prospective follow-up to document major adverse cardiovascular and cerebral events (MACCEs). In vitro experiments were also performed to observe the effects of mtDNA oxidative damage in high glucose-cultured human umbilical vein endothelial cells (HUVECs). RESULTS:Cross-sectionally, greater mtDNA 8-OHdG was associated with increased odds of obstructive CAD (odds ratio [OR] 1.38, 95% CI confidence interval 1.24-1.52), higher degree of coronary stenosis (number of diseased vessels: OR 1.29, 95% CI 1.19-1.41; modified Gensini scores: OR 1.28, 95% CI 1.18-1.39), and higher levels of C-reactive protein (β 0.18, 95% CI 0.06-0.31) after adjusting for confounders. Sensitivity analyses using propensity score matching yielded similar results. Stratification by smoking status showed that the association between mtDNA 8-OHdG and obstructive CAD was most evident in current smokers (Pinteration < 0.01). Prospectively, the adjusted hazards ratio per 1-SD increase in mtDNA 8-OHdG was 1.59 (95% CI 1.33-1.90) for predicting 1-year MACCEs after revascularization. In HUVECs, exposure to antimycin A, an inducer for mtDNA oxidative damage, led to adverse alterations in markers of mitochondrial and endothelia function. CONCLUSION:Greater mtDNA 8-OHdG in leukocytes may serve as an independent risk factor for CAD in patients with T2DM.

Dataset Information

Analysis of circulating ceramides and hexosylceramides in patients with coronary artery disease and type II diabetes mellitus.

Background

Methods

Results

Conclusion

Publications

Analysis of circulating ceramides and hexosylceramides in patients with coronary artery disease and type II diabetes mellitus.

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