Dataset Information

Plasma levels of autophagy regulator Rubicon are inversely associated with acute coronary syndrome.

ABSTRACT:

Background

The discovery of novel biomarkers that improve current cardiovascular risk prediction models of acute coronary syndrome (ACS) is needed for the identification of very high-risk patients and therapeutic decision-making. Autophagy is a highly conserved catabolic mechanism for intracellular degradation of cellular components through lysosomes. The autophagy process helps maintain cardiac homeostasis and dysregulated autophagy has been described in cardiovascular conditions. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) is a key regulator of autophagy with a potential role in cardiac stress.

Objectives

The aims of the present study were to assess whether changes in circulating Rubicon levels are associated with ACS and to evaluate the added value of Rubicon to a clinical predictive risk model.

Methods and results

The study population included ACS patients (n = 100) and control subjects (n = 99) at high to very high cardiovascular risk but without known coronary event. Plasma Rubicon levels were measured in the whole study population by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses established that Rubicon levels were inversely associated with ACS. A receiver operating characteristic curve analysis demonstrated that the addition of Rubicon improved the predictive performance of the model with an increased area under the curve from 0.868 to 0.896 (p = 0.038).

Conclusions

Plasma levels of the autophagy regulator Rubicon are associated with ACS and provide added value to classical risk markers for ACS.

SUBMITTER: Grazide MH

PROVIDER: S-EPMC10796531 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Plasma levels of autophagy regulator Rubicon are inversely associated with acute coronary syndrome.

Grazide Marie-Hélène MH Ruidavets Jean-Bernard JB Martinet Wim W Elbaz Meyer M Vindis Cécile C

Frontiers in cardiovascular medicine 20240105

<h4>Background</h4>The discovery of novel biomarkers that improve current cardiovascular risk prediction models of acute coronary syndrome (ACS) is needed for the identification of very high-risk patients and therapeutic decision-making. Autophagy is a highly conserved catabolic mechanism for intracellular degradation of cellular components through lysosomes. The autophagy process helps maintain cardiac homeostasis and dysregulated autophagy has been described in cardiovascular conditions. Rubic ...[more]

PMID: 38250026

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Project description:BackgroundMicrofibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS.MethodsWe performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan-Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters.ResultsCirculating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p < 0.001). After adjusting for confounding factors, we found that MFAP4 was an independent risk factor for STEMI (odds ratio = 0.395, 95% CI 0.174-0.895, p = 0.026). MFAP4 level was negatively correlated with Gensini score and Syntax score (r = - 0.311 and - 0.211, p < 0.001 and 0.01, respectively). Based on the MFAP4 level of 0.117 ng/ml, ACS patients were divided into two groups: the low-MFAP4 group (< 0.117 ng/ml, n = 60) and the high-MFAP4 group (≥ 0.117 ng/ml, n = 88). After the median follow-up of 165 days, Kaplan-Meier survival analysis revealed that the MACE-free rate was significantly lower in ACS patients with lower MFAP4 levels (p = 0.009).ConclusionsMFAP4 has a potential as a biomarker for the degree of coronary stenosis in ACS. Confirmation of observations in larger cohorts and longer follow-up periods is warranted.

Project description:BackgroundNeutrophils play important roles in atherosclerosis and atherothrombosis. Bactericidal/permeability-increasing protein (BPI) is mainly expressed in the granules of human neutrophils in response to inflammatory stress. This observational, cross-sectional study investigated the plasma level of BPI in patients with acute coronary syndrome (ACS) and its correlation with blood neutrophil counts and circulating inflammatory biomarkers.MethodsA total of 367 patients who had acute chest pain and who were admitted to our hospital for coronary angiography (CAG) and/or percutaneous coronary intervention (PCI) from May 1, 2020 to August 31, 2020 were recruited. Among them, 256 had a cardiac troponin value above the 99th percentile upper reference limit and were diagnosed with ACS. The remaining patients (n = 111) were classified as non-ACS. The TIMI and GRACE scores were calculated at admission. The Gensini score based on CAG was used to determine atherosclerotic burden. Plasma levels of interleukin (IL)-1β, myeloperoxidase-DNA (MPO-DNA), high sensitivity C-reactive protein (hs-CRP), S100A8/A9, and BPI were measured using enzyme-linked immunosorbent assays. Correlations of plasma BPI levels with examination scores and levels of circulating inflammatory biomarkers were explored. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic efficacy of BPI for ACS and myocardial infarction.ResultsPatients in the ACS group showed significantly higher plasma BPI levels compared to the non-ACS group (46.42 ± 16.61 vs. 16.23 ± 6.19 ng/mL, p < 0.05). Plasma levels of IL-1β, MPO-DNA, hs-CRP, and S100A8/A9 in the ACS group were also significantly higher than those in the non-ACS group (all p < 0.05). In addition, plasma BPI levels were positively correlated with the TIMI, GRACE, and Gensini scores (r = 0.176, p = 0.003; r = 0.320, p < 0.001; r = 0.263, p < 0.001, respectively) in patients with ACS. Plasma BPI levels were also positively correlated with blood neutrophil counts (r = 0.266, p < 0.001) and levels of circulating inflammatory biomarkers (IL-1β, r = 0.512; MPO-DNA, r = 0.452; hs-CRP, r = 0.554; S100A8/A9, r = 0.434; all p < 0.001) in patients with ACS. ROC curve analysis revealed that the diagnostic efficacy of BPI for ACS was not inferior to that of IL-1β, MPO-DNA, hs-CRP, S100A8/A9, or blood neutrophil counts. ROC analysis also showed that the diagnostic efficacy of BPI for myocardial infarction was not inferior to that of creatine kinase (CK)-MB or cardiac troponin I.ConclusionBPI is associated with systemic inflammation in ACS and may be involved in the process of atherosclerosis and atherothrombosis. The potential of BPI as a prognostic and diagnostic biomarker for ACS should be investigated in clinical settings.

Dataset Information

Plasma levels of autophagy regulator Rubicon are inversely associated with acute coronary syndrome.

Background

Objectives

Methods and results

Conclusions

Publications

Plasma levels of autophagy regulator Rubicon are inversely associated with acute coronary syndrome.

Similar Datasets

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