Novel Blood Biomarkers for a Diagnostic Workup of Acute Aortic Dissection.
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ABSTRACT:
SUBMITTER: Forrer A
PROVIDER: S-EPMC8065878 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAcute aortic dissection (AAD) is a serious and life-threatening cardiovascular emergency. This study aim to investigate whether MicroRNAs (miRNAs)in circulating exosomes could serve as novel diagnostic biomarkers for AAD.MethodsUsing miRNA microarray sequencing, the differentially expressed exosomal miRNAs between AAD patients and control subjects were found. In this study, we investigated 8 miRNAs (miR-499a-5p/miR-543/miR-143-3p/miR-4433b-3p/miR-744-5p/miR-4488/miR-202-3p/miR-206), 4 Proteins (Matrix Metalloprotein-9/12)/transforming growth factor-β/D-Dimer) in AAD (n = 75) and Control (n = 86) expression levels between the 2 groups. The combined diagnostic of exosomal miRNAs and Proteins was performed (area under curve [AUC] > 0.8, R > 0.5 and P < .01). The Receiver Operating Characteristic curve was drawn to evaluate the diagnostic efficacy. Predict the gene targets of differentially expressed miRNAs and analyze the functions and signaling pathways of these targets using online databases.ResultsThe exosomes isolated from the 2 groups of serum were bilayer membranes with a diameter of about 100 nm. Stably expressed in CD9, CD63 and TSG101. Compared with the control subjects, 8 exosomal miRNAs (miR-499a-5p, miR-543, miR-206, miR-143-3p, miR-4433b-3p, miR-744-5p, miR- 4488, and miR-202-3p) were regulated to varying degrees (P < .05). miR-499a-5p, miR-202-3p, and D-Dimer had higher diagnostic efficacy (AUC > 0.90). Among them, miR-499a-5p had the highest diagnostic accuracy, reaching 95%, AUC = 0.99. Co-diagnosis of positively correlated miRNAs and Proteins improves the diagnostic performance. The combined diagnostic accuracy of miR-499a-5p and miR-202-3p was 98% (AUC = 0.998), and the sensitivity and specificity were 98%. The combined diagnostic accuracy of miR-499a-5p and matrix metalloprotein-9 was 98% (AUC = 0.996), and the sensitivity and specificity were 98%. Gene Ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes signaling pathway analysis, some predicted targets of these miRNAs are involved in the pathophysiological process of AAD.ConclusionSerum exosomal miR-499a-5p, miR-143-3p, and miR-202-3p can be used as potential diagnostic biomarkers for AAD, and the combination of various markers can coordinate and complement each other, and can significantly improve the diagnosis of aortic dissection sensitivity and specificity.
| S-EPMC10378726 | biostudies-literature
Project description:BackgroundAortic dissection (AD) is a serious and fatal vascular disease. The earlier the condition of AD patients can be assessed precisely, the more scientifically controlled the patient's condition will be. Therefore, timely and accurate diagnosis is significant for AD. Blood biomarker testing as a method of liquid biopsy can improve the diagnostic efficiency of AD. This study conducted a systematic review of the current blood diagnostic biomarkers of AD.MethodsThe PubMed, Cochrane Library, Web of Science, and Embase electronic databases were systematically searched from inception to January 1, 2023, using the terms "aortic dissection", "serum", "plasma" and "diagnosis". Stata 12.0 software was used to perform Random effects meta-analysis was performed using Stata 12.0 software to determine the effect sizes and corresponding 95% confidence intervals. Then, a summary receiver operator characteristic (SROC) curve was drawn, and the area under the ROC curve (AUC) was calculated.ResultsD-dimer had the best sensitivity and AUC for AD, with values of 0.96 (95% CI: 0.93-0.98) and 0.95 (95% CI: 0.93-0.97), respectively. The sensitivity and AUC values for D-dimer with a cut-off value of 500 ng/mL were 0.97 (95% CI: 0.95-0.99) and 0.94 (95% CI: 0.92-0.96), respectively. In contrast, microRNA had a better specificity value for AD, at 0.79 (95% CI: 0.73-0.83).ConclusionsD-dimer and microRNA have good accuracy in the diagnosis of AD, but the specificity of D-dimer is worse, and studies of microRNA are insufficient. The combination of different biomarkers can improve the diagnostic accuracy. Other blood biomarkers are related to the pathological progression of AD and can be selected according to pathological progress.
| S-EPMC10563263 | biostudies-literature
Project description:A 77-year-old man presented with acute-onset severe chest pain radiating to the back and elevated blood pressure. Multiphasic computed tomography of the aorta revealed an intimal tear in the descending thoracic aorta which extended both retrograde to the aortic root and antegrade to the infra-renal abdominal aorta. The initial impression, that the images showed a Stanford type B aortic dissection, was because the portion of the false lumen that extended beyond the aortic arch remained unopacified even on delayed phases, making it challenging to assess the extent of the dissection flap. Bedside transthoracic echocardiography revealed a pericardial effusion. Cardiac tamponade ensued and the patient passed away shortly after presentation. This case highlights the need for early and accurate imaging assessment of acute aortic dissection, including accurate identification of the site of intimal tear and the extent of the dissection flap.
| S-EPMC5917054 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a prevalent complication following acute type A aortic dissection (ATAAD) surgery and is closely associated with unfavorable prognostic outcomes. Hence, the development of a robust and efficient diagnostic approach to identify high-risk patients is of paramount importance.MethodsWe conducted a prospective study involving 328 patients who underwent ATAAD surgery at our institution, comprising three distinct cohorts. In addition, 52 patients undergoing alternative cardiopulmonary surgeries and 37 healthy individuals were enrolled as control groups. Employing proteomic analysis, we initially identified plasma proteins potentially linked to AKI occurrence within the plasma proteomic cohort. Subsequent validation was performed in an independent cohort. Utilizing predictors derived from multivariate logistic regression analysis, a nomogram was meticulously formulated and its efficacy was validated in the model construction cohort.ResultsProteomics revealed significant elevation of plasma levels of S100A8/A9, pentraxin 3 (PTX3), and chitinase 3-like 1 (CHI3L1) immediately post-surgery in patients who developed ATAAD surgery-associated AKI (ASA-AKI). Receiver operating characteristic (ROC) curves demonstrated impressive predictive performance of S100A8/A9, PTX3, and CHI3L1 at 0 h post-surgery, yielding area under the curve (AUC) values of 0.823, 0.786, and 0.803, respectively, for ASA-AKI prediction. Furthermore, our findings exhibited positive correlations between plasma levels of S100A8/A9, PTX3, CHI3L1, and urinary neutrophil gelatinase-associated lipocalin (NGAL) at 0 h post-surgery, along with correlations between plasma S100A8/A9, CHI3L1 levels, and the Cleveland Clinic score. A logistic regression model incorporating plasma S100A8/A9, PTX3, CHI3L1 levels, urinary NGAL levels, and the Cleveland Clinic score facilitated the construction of a predictive nomogram for ASA-AKI. This nomogram demonstrated robust discriminative ability, achieving an AUC of 0.963 in the model construction cohort.ConclusionsOur study underscored the augmentation of plasma S100A8/A9, PTX3, and CHI3L1 levels immediately post-surgery in patients developing ASA-AKI. The incorporation of these three biomarkers, in conjunction with the Cleveland Clinic score and NGAL, into a nomogram demonstrated commendable predictive efficacy. This presents a practical tool for identifying patients at an elevated risk of AKI following ATAAD surgery.
| S-EPMC10729328 | biostudies-literature
Project description:Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R2X = 0.362 and R2Y = 0.807, p = 0.03) and predictability (Q2 = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256-7.245, p = 0.035; OR = 0.015, 95%CI:0.0002-0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.
| S-EPMC9324768 | biostudies-literature
Project description:The purpose of this study was to evaluate the utility of potential serum biomarkers for acute aortic dissection (AAD) that were identified by isobaric Tags for Relative and Absolute Quantitation (iTRAQ) approaches. Serum samples from 20 AAD patients and 20 healthy volunteers were analyzed using iTRAQ technology. Protein validation was performed using samples from 120 patients with chest pain. A total of 355 proteins were identified with the iTRAQ approach; 164 proteins reached the strict quantitative standard, and 125 proteins were increased or decreased more than 1.2-fold (64 and 61 proteins were up- and downregulated, resp.). Lumican, C-reactive protein (CRP), thrombospondin-1 (TSP-1), and D-dimer were selected as candidate biomarkers for the validation tests. Receiver operating characteristic (ROC) curves show that Lumican and D-dimer have diagnostic value (area under the curves [AUCs] 0.895 and 0.891, P < 0.05). For Lumican, the diagnostic sensitivity and specificity were 73.33% and 98.33%, while the corresponding values for D-dimer were 93.33% and 68.33%. For Lumican and D-dimer AAD combined diagnosis, the sensitivity and specificity were 88.33% and 95%, respectively. In conclusion, Lumican has good specificity and D-dimer has good sensitivity for the diagnosis of AAD, while the combined detection of D-dimer and Lumican has better diagnostic value.
| S-EPMC4925974 | biostudies-literature
Project description:Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for initiation of treatment and improved survival. However, identification of biomarkers for AAD in blood is a challenging task. The present study aims to find the potential AAD biomarkers using a transcriptomic strategy. Arrays based genome-wide gene expression profiling were performed using ascending aortic tissues which were collected from AAD patients and healthy donors. The differentially expressed genes were validated using quantitative reverse transcriptase PCR (qRT-PCR) and western blot. The plasma levels of a potential biomarker, angiopoietin 2 (ANGPT2) were determined in case-control cohort (77 AAD patients and 82 healthy controls) by enzyme linked immunosorbent assay. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic power of ANGPT2 for AAD. Transcriptome data demonstrated that a total of 18 genes were significantly up-regulated and 28 genes were significantly down-regulated among AAD tissues (foldchange>3.0, p < 0.01). By bioinformatic analysis, we identified ANGPT2 as a candidate biomarker for blood-based detection of AAD. The qRT-PCR and protein expression demonstrated that ANGPT2 increased 2.4- and 4.2 folds, respectively in aortic tissue of AAD patients. Immunohistochemical staining demonstrated that ANGPT2 was markedly increased in intima of the aortic wall in AAD. Furthermore, ANGPT2 was significantly elevated in AAD patients as compared with controls (median 1625 vs. 383 pg/ml, p < 1E-6). ROC curve analysis showed that ANGPT2 was highly predictive of a diagnosis of type A AAD (area under curve 0.93, p < 1E-6). Sensitivity and specificity were 81 and 90%, respectively at the cutoff value of 833 pg/ml. In conclusion, ANGPT2 could be a promising biomarker for diagnosis of AAD; however, more studies are still needed to verify its specificity in diagnosing of AAD.
| S-EPMC8733161 | biostudies-literature
Project description:Early and convenient diagnosis is urgently needed for acute Stanford type A aortic dissection (AAAD) patients due to its high mortality within the first 48?hours. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular diseases, however, little is known about circulating miRNAs involved in AAAD. Here, the blood serum was sampled from 104 AAAD+ patients and 103 age-matched donors. Initial screening was conducted using the TaqMan Low Density Array followed by RT-qPCR confirmation. According to the two-phase selection and validation process, we found that miR-25, miR-29a and miR-155 were significantly elevated, while miR-26b was markedly decreased in AAAD+ serum samples compared with AAAD- individuals. Most importantly, for individuals with hypertension, which is a major contributor to AAAD, the 4-miRNA panel also showed high accuracy in predicting those who are more likely to develop AAAD. In the blind trial set, the panel correctly classified 93.33% AAAD+ patients and 86.67% controls from the hypertension cohort. Finally, the serum miRNA-based biomarker for early AAAD detection was supported by a retrospective analysis. Taken together, we identify a distinct profile of 4-miRNA that can serve as a noninvasive biomarker for AAAD diagnosis, especially for those with hypertension.
| S-EPMC5651857 | biostudies-other
Project description:Stanford type A aortic dissection (AD) is a lethal disease requiring surgery. Evidence regarding the prognostic ability of perioperative myocardiac markers on long-term outcome is limited.In this cohort study, we measured perioperative myocardiac markers level in 583 surgical patients with type A AD in our hospital between 2015 and 2017. All patients were followed up after surgery for a median period of 864 days to determine short- and long-term mortality.About one-fifth of patients has a positive preoperative myocardial markers, which was increased significantly after operation. Increase log10 post-creatine kinase MB isoenzyme (CK-MB) (hazard ratio [HR], 4.64; 95% confidence interval [CI] 1.89-11.43; P = .0008), log10 post-TnI (HR, 3.11; 95% CI 1.56-6.21; P = .0013), log10 post-Mb (HR, 3.00; 95% CI 1.40-6.43; P = .0048), log10 pre-CK-MB (HR,1.82; 95% CI 1.03-3.21; P = .0377), and upper tertile of post-CK-MB (HR,1.52; 95% CI 1.05-2.20; P = .0261) were the independent risk factor for 30 days mortality adjusted for potential confounders. None of cardiac markers was significantly associated with long-term outcome independent of other factors.Perioperative myocardiac predicts early outcome in type A AD patients undergoing surgery. Increasing perioperative myocardial markers do not appear to be a predictor for long-term all-cause mortality.
| S-EPMC6824686 | biostudies-literature
Project description:Aortic dissection may induce a systemic inflammatory reaction. The etiological backgrounds for elevation of the white blood cell count remain to be clarified. In 466 patients with acute type A aortic dissection treated surgically within 48 hours of symptom onset, the etiologic background of an elevated admission white blood cell count and the effect of such elevation on outcomes were assessed retrospectively. Patients' white blood cell count differed significantly in relation to the extent of dissection, with a median (25th, 75th percentile) white blood cell count of 10.4 (8.1, 13.9) x 103/?L for dissection confined to the ascending aorta, 10.5 (8.2,13.) 103/?L for dissection extending to the aortic arch/descending aorta, 11.1 (8.2, 13.7) x 103/?L for extension to the abdominal aorta, and 13.3 (9.8, 15.9) x 103/?L for extension to the iliac artery (p<0.001). With 11.0 x 103/?L used as the cut-off value for white blood cell count elevation, multivariable analysis showed current smoking (p<0.001; odds ratio, 2.79), dissection extending to the iliac artery (p = 0.006; odds ratio, 1.79), age (p = 0.007, odds ratio, 0.98), and no coronary ischemia (p = 0.027, odds ratio, 2.22) to be factors related to the elevated white blood cell count. Mean age differed significantly between patients with and without an elevated white blood cell count (62.3 vs. 68.3 years, p <0.001). Although in-hospital mortality was similar (7.5% vs.10.9%, p = 0.19), 5-year survival was lower in patients without an elevated count (85.7% vs. 78.6%, p = 0.019), reflecting their more advanced age. In conclusion, our data suggest that dissection morphology and patient age influence the acute phase systemic inflammatory response associated with an elevated white blood cell count in patients with ATAAD. A better understanding of this relation may help optimize diagnosis and perioperative care.
| S-EPMC7004339 | biostudies-literature