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Identified plasma proteins related to vascular structure are associated with coarctation of the aorta in children.

ABSTRACT: BACKGROUND:Coarctation of the aorta (CoA), presenting with local stenosis of the aorta is involved in many cardiovascular processes. However, there has been little research on the mechanism of coarctation of the aorta. METHODS:Altered proteins were identified by isobaric tag for relative and absolute quantitation (iTRAQ) technology in 8 participants, and further analysed by heatmap, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Search Tool for the Retrieval of Interacting Gene (STRING). Of these, two vascular structure-related proteins were further validated by using enzyme-linked immunosorbent assay (ELISA) in a new cohort of CoA patients. RESULTS:39 differentially expressed plasma proteins were first identified in patients with coarctation of the aorta by iTRAQ. Of these, fibulin-1 (FBLN1) and insulin-like growth factor-binding protein complex acid labile subunit (ALS) were considered candidates and further validation also showed that the level of FBLN1 in the CoA group (8.92?±?2.36??g/ml) was significantly higher compared with control group (6.13?±?1.94??g/ml), and the level of ALS in CoA children (348.08?±?216.74?ng/ml) was significantly lower than the level in normal children (619.46?±?274.08?ng/ml). CONCLUSIONS:The differentially expressed proteins identified in the plasma from CoA patients indicated that they may play critical roles in CoA and that they could potentially be utilized as biomarkers for diagnosis. Altered vascular related proteins were associated with COA. These results provide a foundation for further understanding and studying the aetiology and pathogenesis of coarctation of the aorta.

SUBMITTER: Ma S

PROVIDER: S-EPMC7236479 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Identified plasma proteins related to vascular structure are associated with coarctation of the aorta in children.

Ma Siyu S Zheng Junqiang J Xu Yang Y Yang Zhaocong Z Zhu Yu Y Su Xiaoqi X Mo Xuming X

Italian journal of pediatrics 20200519 1

<h4>Background</h4>Coarctation of the aorta (CoA), presenting with local stenosis of the aorta is involved in many cardiovascular processes. However, there has been little research on the mechanism of coarctation of the aorta.<h4>Methods</h4>Altered proteins were identified by isobaric tag for relative and absolute quantitation (iTRAQ) technology in 8 participants, and further analysed by heatmap, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Search Tool for the ...[more]

PMID: 32430056

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Project description:Background Optimally treated patients with coarctation of the aorta remain at risk for late vascular dysfunction. The effect of treatment modality on vascular function is unknown. The LOVE-COARCT (Long-term Outcomes and Vascular Evaluation After Successful Coarctation of the Aorta Treatment) study was done to compare vascular function in patients with coarctation of the aorta treated with surgery, balloon dilation (BD), or stent implantation. Methods and Results In treated coarctation of the aorta patients without residual coarctation, we prospectively compared aortic stiffness by applanation tonometry and cardiac magnetic resonance; endothelial function by endothelial pulse amplitude testing; blood pressure ( BP ) phenotype by office BP , ambulatory BP monitoring, and BP response to exercise; left ventricular mass by cardiac magnetic resonance; and blood biomarkers of endothelial function, inflammation, vascular wall function, and extracellular matrix. Participants included 75 patients treated with surgery (n=28), BD (n=23), or stent (n=24). Groups had similar age at enrollment, coarctation of the aorta severity, residual gradient, and metabolic profile, but differed by age at treatment. Prevalence of systemic hypertension, aortic stiffness, endothelial function, and left ventricular mass were similar among treatment groups. However, BD patients had more-distensible ascending aortas, lower peak systolic BP during exercise, less impairment in diurnal BP variation, and lower inflammatory biomarkers. Results were unchanged after adjustment for potential confounders, including age at treatment. Conclusions In our cohort of patients without residual coarctation, treatment modality was not associated with major vascular outcomes, even though there were some favorable vascular characteristics in the BD patients. Although this suggests that choice of treatment modality should continue to be driven by likelihood of achieving a good anatomical result, more long-term studies are required to assess the clinical significance of the more-optimal results of secondary markers of vascular function in BD patients. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03262753.

Project description:BackgroundCoarctation of the aorta is a common form of critical congenital heart disease that remains challenging to diagnose prior to clinical deterioration. Despite current screening methods, infants with coarctation may present with life-threatening cardiogenic shock requiring urgent hospitalization and intervention. We sought to improve critical congenital heart disease screening by using a novel pulse oximetry waveform analysis, specifically focused on detection of coarctation of the aorta.Methods and resultsOver a 2-year period, we obtained pulse oximetry waveform data on 18 neonates with coarctation of the aorta and 18 age-matched controls hospitalized in the cardiac intensive care unit at Children's Healthcare of Atlanta. Patients with coarctation were receiving prostaglandin E1 and had a patent ductus arteriosus. By analyzing discrete features in the waveforms, we identified statistically significant differences in the maximum rate of fall between patients with and without coarctation. This was accentuated when comparing the difference between the upper and lower extremities, with the lower extremities having a shallow slope angle when a coarctation was present (p-value 0.001). Postoperatively, there were still differences in the maximum rate of fall between the repaired coarctation patients and controls; however, these differences normalized when compared with the same individual's upper vs. lower extremities. Coarctation patients compared to themselves (preoperatively and postoperatively), demonstrated waveform differences between upper and lower extremities that were significantly reduced after successful surgery (p-value 0.028). This screening algorithm had an accuracy of detection of 72% with 0.61 sensitivity and 0.94 specificity.ConclusionsWe were able to identify specific features in pulse oximetry waveforms that were able to accurately identify patients with coarctation and further demonstrated that these changes normalized after surgical repair. Pulse oximetry screening for congenital heart disease in neonates may thus be improved by including waveform analysis, aiming to identify coarctation of the aorta prior to critical illness. Further large-scale testing is required to validate this screening model among patients in a newborn nursery setting who are low risk for having coarctation.

Project description:BackgroundThe term vitamin E describes a family of 8 vitamers, 1 of which is α-tocopherol, that is essential for human health. Vitamin E status remains largely unknown in low-income countries because of the complexity and cost of measurement. Quantitative proteomics may offer an approach for identifying plasma proteins for assessing vitamin E status in these populations.ObjectiveTo improve options for vitamin E status assessment, we sought to detect and quantify a set of plasma proteins associated with α- and γ-tocopherol concentrations in a cohort of 500 rural Nepalese children aged 6-8 y and, based on nutrient-protein associations, to predict the prevalence of vitamin E deficiency (α-tocopherol <12 μmol/L).MethodsStudy children were born to mothers enrolled in an earlier antenatal micronutrient trial in Sarlahi District, Nepal. Plasma α- and γ-tocopherol concentrations were measured by high-performance liquid chromatography. Plasma aliquots were depleted of 6 high-abundance proteins, digested with trypsin, labeled with isobaric mass tags, and assessed for relative protein abundance by tandem mass spectrometry. Linear mixed-effects models were used to evaluate the association between α-tocopherol status and relative protein abundance and to predict deficiency.ResultsWe quantified 982 plasma proteins in >10% of all child samples, of which 119 correlated with α-tocopherol (false discovery rate, q < 0.10). Proteins were primarily involved in lipid transport, coagulation, repair, innate host defenses, neural function, and homeostasis. Six proteins [apolipoprotein (apo)C-III; apoB; pyruvate kinase, muscle; forkhead box 04; unc5 homolog C; and regulator of G-protein signaling 8] explained 71% of the variability in plasma α-tocopherol, predicting an in-sample population prevalence of vitamin E deficiency of 51.4% (95% CI: 46.4%, 56.3%) compared with a measured prevalence of 54.8%. Plasma γ-tocopherol was associated with 12 proteins (q < 0.10), 2 of which (apoC-III and Misato 1) explained 20% of its variability.ConclusionsIn this undernourished population of children in South Asia, quantitative proteomics identified a large plasma α-tocopherome from which 6 proteins predicted the prevalence of vitamin E deficiency. The findings illustrate that protein biomarkers, once absolutely quantified, can potentially predict micronutrient deficiencies in populations. The maternal micronutrient supplementation trial from which data were derived as a follow-up activity was registered with clinicaltrials.gov as NCT00115271.

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Identified plasma proteins related to vascular structure are associated with coarctation of the aorta in children.

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Identified plasma proteins related to vascular structure are associated with coarctation of the aorta in children.

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