Metabolomic fingerprint of coronary blood in STEMI patients depends on the ischemic time and inflammatory state.
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ABSTRACT:
SUBMITTER: Deidda M
PROVIDER: S-EPMC6342950 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe endothelium is a key variable in the pathogenesis of atherosclerosis and its complications, particularly coronary artery disease (CAD). Current evidence suggests that the endothelial status can be regarded as an integrated index of individual atherogenic and anti-atherogenic properties, and that the interaction between circulating factors and the arterial wall might be critical for atherogenesis. In organism-level investigations, a functional view is provided by metabolomics, the study of the metabolic profile of small molecules. We sought to verify whether metabolomic analysis can reveal the presence of coronary microenvironment peculiarities associated with distinct manifestations of CAD.MethodsThirty-two coronary blood samples were analyzed using 1H-NMR-based metabolomics. Samples collected from patients with evidence of myocardial ischemia formed the case group, and were further divided into the stenotic-disease (SD) group (N = 13) and absence of stenosis (microvascular disease; "Micro") group (N = 8); specimens of patients presenting no evidence of ischemic heart disease (dilated cardiomyopathy, valvular diseases) constituted the control group (N = 11).ResultsApplication of an orthogonal partial least squares discriminant analysis (OPLS-DA) model to the entire dataset clearly separated the samples into 3 groups, indicating 3 distinct metabolic fingerprints. Relative to control-group members, Micro patients showed a higher content of 2-hydroxybutirate, alanine, leucine, isoleucine, and N-acetyl groups and lower levels of creatine/phosphocreatine, creatinine, and glucose, whereas SD patients showed higher levels of 3-hydroxybutirate and acetate and a lower content of 2-hydroxybutirate. Moreover, relative to SD patients, Micro patients showed higher levels of 2-hydroxybutirate, alanine, leucine, and N-acetyl groups and lower levels of 3-hydroxybutirate and acetate.ConclusionsSpecific coronary microenvironments are likely associated with distinct development and pathological expression of CAD.
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Project description:Contemporary metabolomic fingerprinting is based on multiple spectrometric and chromatographic signals, used either alone or combined with structural and chemical information of metabolic markers at the qualitative and semiquantitative level. However, signal shifting, convolution, and matrix effects may compromise metabolomic patterns. Recent increase in the use of qualitative metabolomic data, described by the presence (1) or absence (0) of particular metabolites, demonstrates great potential in the field of metabolomic profiling and fingerprint analysis.The aim of this study is a comprehensive evaluation of binary similarity measures for the elucidation of patterns among samples of different botanical origin and various metabolomic profiles.Nine qualitative metabolomic data sets covering a wide range of natural products and metabolomic profiles were applied to assess 44 binary similarity measures for the fingerprinting of plant extracts and natural products. The measures were analyzed by the novel sum of ranking differences method (SRD), searching for the most promising candidates.Baroni-Urbani-Buser (BUB) and Hawkins-Dotson (HD) similarity coefficients were selected as the best measures by SRD and analysis of variance (ANOVA), while Dice (Di1), Yule, Russel-Rao, and Consonni-Todeschini 3 ranked the worst. ANOVA revealed that concordantly and intermediately symmetric similarity coefficients are better candidates for metabolomic fingerprinting than the asymmetric and correlation based ones. The fingerprint analysis based on the BUB and HD coefficients and qualitative metabolomic data performed equally well as the quantitative metabolomic profile analysis.Fingerprint analysis based on the qualitative metabolomic profiles and binary similarity measures proved to be a reliable way in finding the same/similar patterns in metabolomic data as that extracted from quantitative data.
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Project description:Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes in the blood. Although less relevant to the study of psoriasis pathogenesis, blood transcriptome profiles can be readily compared across various diseases. Here, we used a pre-established set of 382 transcriptional modules as a common framework to compare changes in blood transcript abundance in two independent public psoriasis datasets. We then compared the resulting "transcriptional fingerprints" to those obtained for a reference set of 16 pathological or physiological states. The perturbations in blood transcript abundance in psoriasis were relatively subtle compared to the changes we observed in other autoimmune and auto-inflammatory diseases. However, we did observe a consistent pattern of changes for a set of modules associated with neutrophil activation and inflammation; interestingly, this pattern resembled that observed in patients with Kawasaki disease. This similarity between the blood-transcriptome signatures in psoriasis and Kawasaki disease suggests that the immune mechanisms driving their pathogenesis might be partially shared.
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Project description:We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI)
2015-05-23 | GSE61144 | GEO
Project description:We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI) We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: a set of blood samples of patients with STEMI (n=7) before and 7 days after the primary percutaneous coronary intervention (n=7) and normal control (n=10)
2015-05-23 | E-GEOD-61144 | biostudies-arrayexpress
Project description:BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis.Methods and resultsAmbulatory patients with clinical diagnosis of HFpEF (n = 24), HFrEF (n = 20), and age-matched non-HF controls (n = 38) were selected for metabolomic analysis as part of the Alberta HEART (Heart Failure Etiology and Analysis Research Team) project. 181 serum metabolites were quantified by LC-MS/MS and 1H-NMR spectroscopy. Compared to non-HF control, HFpEF patients demonstrated higher serum concentrations of acylcarnitines, carnitine, creatinine, betaine, and amino acids; and lower levels of phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Medium and long-chain acylcarnitines and ketone bodies were higher in HFpEF than HFrEF patients. Using logistic regression, two panels of metabolites were identified that can separate HFpEF patients from both non-HF controls and HFrEF patients with area under the receiver operating characteristic (ROC) curves of 0.942 and 0.981, respectively.ConclusionsThe metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients.Clinical trial registrationClinicalTrials.gov NCT02052804.
| S-EPMC4444296 | biostudies-literature
Project description:The decisions animals make to adjust their antipredator behavior to rapidly changing conditions have been well studied. Inducible defenses in plants are an antipredator behavior that acts on a longer time scale, but sensitive plants, Mimosa pudica, have a much more rapid antipredator response; they temporarily close their leaves when touched. The time they remain closed is defined as hiding time. We studied hiding time in sensitive plants and found that individual plants differed significantly in their hiding times. We then showed that the effect of individual explained substantial variation in hiding time on a short time scale. Finally, on a longer time scale, individuality persisted but the amount of variation attributed to individual decreased. We hypothesized that variation in plant condition might explain this change. We therefore manipulated sunlight availability and quantified hiding time. When deprived of light for 6 h, sensitive plants significantly shortened their hiding times. But when only half a plant was deprived of light, hiding times on the deprived half and light exposed half were not significantly different. This suggests that overall condition best explains variation in sensitive plant antipredator behavior. Just like in animals, sensitive plant antipredator behavior is condition dependent, and, just like in animals, a substantial amount of the remaining variation is explained by individual differences between plants. Thus, models designed to predict plasticity in animal behavior may be successfully applied to understand behavior in other organisms, including plants.
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Project description:High flavonoid consumption can improve vascular health. Exploring flavonoid-metabolome relationships in population-based settings is challenging, as: (i) there are numerous confounders of the flavonoid-metabolome relationship; and (ii) the set of dependent metabolite variables are inter-related, highly variable and multidimensional. The Metabolite Fingerprint Score has been developed as a means of approaching such data. This study aims to compare its performance with that of more traditional methods, in identifying the metabolomic fingerprint of high and low flavonoid consumers. This study did not aim to identify biomarkers of intake, but rather to explore how systemic metabolism differs in high and low flavonoid consumers. Using liquid chromatography-tandem MS, 174 circulating plasma metabolites were profiled in 584 men and women who had complete flavonoid intake assessment. Participants were randomised to one of two datasets: (a) training dataset, to determine the models for the discrimination variables (n 399); and (b) validation dataset, to test the capacity of the variables to differentiate higher from lower total flavonoid consumers (n 185). The stepwise and full canonical variables did not discriminate in the validation dataset. The Metabolite Fingerprint Score successfully identified a unique pattern of metabolites that discriminated high from low flavonoid consumers in the validation dataset in a multivariate-adjusted setting, and provides insight into the relationship of flavonoids with systemic lipid metabolism. Given increasing use of metabolomics data in dietary association studies, and the difficulty in validating findings using untargeted metabolomics, this paper is of timely importance to the field of nutrition. However, further validation studies are required.
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Project description:This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.
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Project description:Background and aimsAtherosclerosis is an inflammatory disease with long-lasting activation of innate immunity and monocytes are the main blood cellular effectors. We aimed to investigate monocyte phenotype (subset fraction and marker expression) at different stages of coronary atherosclerosis in stable coronary artery disease (CAD) patients.Methods73 patients with chronic coronary syndrome were evaluated by CT coronary angiography (CTCA) and classified by maximal diameter stenosis of major vessels into three groups of CAD severity: CAD1 (no CAD/minimal CAD, n° = 30), CAD2 (non-obstructive CAD, n° = 21), and CAD3 (obstructive CAD, n° = 22). Flow cytometry for CD14, CD16, and CCR2 was used to quantify Mon1, Mon2, and Mon3 subsets. Expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, and CXCR4 was also measured. Adhesion molecules and cytokines were quantified by ELISA.ResultsTotal cell count and fraction of Mon2 were higher in CAD2 and CAD3 compared to CAD1. By multivariate regression analysis, Mon2 cell fraction and Mon2 expression of CX3CR1, CD18, and CD16 showed a statistically significant and independent increase, parallel to stenosis severity, from CAD1 to CAD2 and CAD3 groups. A similar trend was also present for CX3CR1 and HLA-DR expressions on total monocyte population. A less calcified plaque composition was associated to a higher Mon2 expression of CD16 and higher TNF-α levels. IL-10 levels were lower at greater stenosis severity, while the IFN-γ/IL-10 ratio, a marker of a systemic pro-inflammatory imbalance, was directly correlated to stenosis degree and number of noncalcified plaques.ConclusionsThe results of this study suggest that a specific pattern of inflammation-correlated monocyte marker expression is associated to higher stenosis severity and less calcified lesions in stable CAD. The clinical trial Identifier is NCT04448691.
| S-EPMC7403909 | biostudies-literature