Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach

Shin, Miji; Mun, Sora; Park, Sang Hyun; Lee, Jiyeong; Kang, Hee-Gyoo

doi:10.1042/bsr20210344

Cited by 9 publications

(8 citation statements)

References 71 publications

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“…Several bioinformatic analyses have shown that LRG1 may serve as a useful biomarker in cardiovascular diseases ( 20 – 23 ). For instance, one study demonstrated that LRG1 is elevated in patients with acute coronary syndrome compared with healthy controls ( 20 ). Another proteomic analysis revealed that LRG1 may be a potential biomarker for early diagnosis of heart failure ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, plasma LRG1 was elevated from admission to D1, and then gradually decreased until D30 in patients with STEMI. The possible explanations might be as follows: (1) LRG1, as a vasculopathy factor, is positively associated with abnormal angiogenesis and acute inflammation; meanwhile, the latter factors are enhanced in patients with STEMI ( 11 , 20 ). Hence, plasma LRG1 was increased in patients with STEMI compared with healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…Several bioinformatic analyses have shown that LRG1 may serve as a useful biomarker in cardiovascular diseases (20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

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Plasma leucine-rich α-2 glycoprotein 1 in ST-elevation myocardial infarction: vertical variation, correlation with T helper 17/regulatory T ratio, and predictive value on major adverse cardiovascular events

Luo,

Jiang,

Zhang

et al. 2024

Front. Cardiovasc. Med.

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ObjectiveLeucine-rich α-2 glycoprotein 1 (LRG1) promotes inflammation and myocardial injury, but its clinical role in ST-elevation myocardial infarction (STEMI) is rarely disclosed. Herein, this prospective study aimed to explore the value of plasma LRG1 at different time points to predict major adverse cardiovascular event (MACE) risk in patients with STEMI.MethodsIn total, 209 patients with STEMI were enrolled for determining plasma LRG1 at admission and on day (D)1/D7/D30 after admission via enzyme-linked immunosorbent assay, as well as for determination of peripheral blood T helper 17 (Th17) cells and regulatory T (Treg) cells by flow cytometry. In addition, plasma LRG1 was obtained from 30 healthy controls at enrollment.ResultsLRG1 was increased in patients with STEMI at admission compared with healthy controls (P < 0.001). In patients with STEMI, LRG1 varied at different time points (P < 0.001), which elevated from admission to D1, and gradually declined thereafter. LRG1 at admission was positively associated with Th17 cells (P = 0.001) and Th17/Treg ratio (P = 0.014). LRG1 at admission (P = 0.013), D1 (P = 0.034), D7 (P = 0.001), and D30 (P = 0.010) were increased in patients with MACE compared with those without. LRG1 at D7 exhibited good ability to estimate MACE risk (area under curve = 0.750, 95% confidence interval = 0.641–0.858). LRG1 at admission > 60 μg/ml (P = 0.031) and D7 > 60 μg/ml (P = 0.018) were linked with increased accumulating MACE. Importantly, LRG1 at D7 > 60 μg/ml was independently correlated with increased MACE risk (hazard ratio = 5.216, P = 0.033).ConclusionPlasma LRG1 increases from admission to D1 and gradually declines until D30, which positively links with Th17 cells and MACE risk in patients with STEMI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Plasma leucine-rich α-2 glycoprotein 1 in ST-elevation myocardial infarction: vertical variation, correlation with T helper 17/regulatory T ratio, and predictive value on major adverse cardiovascular events

Luo,

Jiang,

Zhang

et al. 2024

Front. Cardiovasc. Med.

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“…Mass spectrometry‐based methods have been used to identify novel plasma biomarkers of acute atherothrombosis using a two‐step approach of unbiased proteomic discovery analysis in a smaller sample set, followed by targeted validation of selected markers in a larger sample set. Shin et al used LC‐MS/MS in a discovery proteomics analysis of plasma from 50 patients with acute coronary syndrome (ACS) and 50 controls, followed by validation in 120 ACS and 120 controls by targeted MS proteomics for absolute quantification of seven identified top candidates, 96 replicating four (AGP1, C5, LRG1, vitronectin) as significantly increased and one (gelsolin) as decreased in ACS. All four upregulated proteins are expressed predominantly in liver, not myocardium, and thus possibly linked to the pathogenic mechanisms in the acute arterial thrombotic event, rather than reflecting cardiomyocyte injury.…”

Section: Plasma Proteomics In Atherothrombosismentioning

confidence: 99%

Proteomics in thrombosis research

Edfors

Iglesias

Butler

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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A State of the Art lecture titled “Proteomics in Thrombosis Research” was presented at the ISTH Congress in 2021. In clinical practice, there is a need for improved plasma biomarker‐based tools for diagnosis and risk prediction of venous thromboembolism (VTE). Analysis of blood, to identify plasma proteins with potential utility for such tools, could enable an individualized approach to treatment and prevention. Technological advances to study the plasma proteome on a large scale allows broad screening for the identification of novel plasma biomarkers, both by targeted and nontargeted proteomics methods. However, assay limitations need to be considered when interpreting results, with orthogonal validation required before conclusions are drawn. Here, we review and provide perspectives on the application of affinity‐ and mass spectrometry‐based methods for the identification and analysis of plasma protein biomarkers, with potential application in the field of VTE. We also provide a future perspective on discovery strategies and emerging technologies for targeted proteomics in thrombosis research. Finally, we summarize relevant new data on this topic, presented during the 2021 ISTH Congress.

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“…1 Clinical categorization of ACS includes unstable angina pectoris (uAP), ST-segment elevation myocardial infarction (STEMI) and Non-STEMI (NSTEMI). 2 While uAP was traditionally defined as ACS without an elevation in cardiac enzymes, 3 this view has been changed since the introduction of novel high-sensitivity cardiac troponin assay (hs-cTnT) assays. 4 The hs-assays can detect cTnT elevations at concentrations 10–100-fold lower compared to conventional assays, 5 resulting in improved acute myocardial infarction (AMI) detection and identification of smaller infarcts previously misdiagnosed as uAP.…”

Section: Introductionmentioning

confidence: 99%

Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of acute coronary syndrome

Koch,

García-Hidalgo,

Labus

et al. 2024

Preprint

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AimLong noncoding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers owing to their dynamic regulation in response to pathological conditions and their detection in clinically relevant samples. Here, we explored the utility of the cardiac expressed and plasma detectable lncRNA PDE4DIPP6 as a biomarker for acute coronary syndrome (ACS). The final goal was to improve the diagnostic efficacy of state-of-the-art tests, particularly the high-sensitivity cardiac troponin assay (hs-cTnT).MethodsThe study enrolled individuals presenting with suspected ACS at the emergency department (ED). LncRNA quantification was performed in plasma samples using RT-qPCR. Discriminatory performance was evaluated by calculating the Area Under the Curve (AUC). Reclassification metrics, including the Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) indexes, were employed to assess enhancements in diagnostic accuracy.ResultsThe sample comprised 252 patients, 50.8% were diagnosed with ACS and 13.9% with Non-ST Segment Elevation Myocardial Infarction (NSTEMI). Elevated levels of PDE4DIPP6 were observed in ACS patients compared to non-ACS subjects. There was no significant correlation between lncRNA and hs-cTnT levels (rho=0.071), and no association between PDE4DIPP6 levels and potential confounding factors was observed. The inclusion of PDE4DIPP6 on top of troponin T significantly enhanced the discrimination and classification of ACS patients reflected in an improved AUC of 0.734, an IDI of 0.066 and NRI of 0.471. Similarly, elevated levels of the lncRNA were observed in NSTEMI patients compared to ACS patients without NSTEMI. Consistent with previous findings, the addition of PDE4DIPP6 to hs-cTnT improved the discrimination and classification of patients, evident in an increased AUC from 0.859 to 0.944, IDI of 0.237, and NRI of 0.658.ConclusionPDE4DIPP6 offers additional diagnostic insights beyond hs-cTnT, suggesting its potential to improve the clinical management of patients with ACS.

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Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach

Cited by 9 publications

References 71 publications

Plasma leucine-rich α-2 glycoprotein 1 in ST-elevation myocardial infarction: vertical variation, correlation with T helper 17/regulatory T ratio, and predictive value on major adverse cardiovascular events

Plasma leucine-rich α-2 glycoprotein 1 in ST-elevation myocardial infarction: vertical variation, correlation with T helper 17/regulatory T ratio, and predictive value on major adverse cardiovascular events

Proteomics in thrombosis research

Circulating long noncoding RNA PDE4DIPP6: A novel biomarker for improving the clinical management of acute coronary syndrome

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