scholarly journals Retinol‐Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3

2021 ◽  
Author(s):  
Kang‐Zhen Zhang ◽  
Xi‐Yu Shen ◽  
Man Wang ◽  
Li Wang ◽  
Hui‐Xian Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Binding Protein ◽  
Cardiac Injury ◽  
Retinol Binding Protein ◽  
Artery Ligation ◽  
Retinol Binding Protein 4 ◽  
Pyrin Domain ◽  
Injury Model ◽  
Cardiovascular Morbidity And Mortality ◽  
Underlying Mechanisms

Background Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular morbidity and mortality worldwide. Pyroptosis is a form of inflammatory cell death that plays a major role in the development and progression of cardiac injury in AMI. However, the underlying mechanisms for the activation of pyroptosis during AMI are not fully elucidated. Methods and Results Here we show that RBP4 (retinol‐binding protein 4), a previous identified proinflammatory adipokine, was increased both in the myocardium of left anterior descending artery ligation‐induced AMI mouse model and in ischemia‐hypoxia‒induced cardiomyocyte injury model. The upregulated RBP4 may contribute to the activation of cardiomyocyte pyroptosis in AMI because overexpression of RBP4 activated NLRP3 (nucleotide‐binding oligomerization domain‐like receptor family pyrin domain‐containing 3) inflammasome, promoted the precursor cleavage of Caspase‐1, and subsequently induced GSDMD (gasdermin‐D)‐dependent pyroptosis. In contrast, knockdown of RBP4 alleviated ischemia‐hypoxia‒induced activation of NLRP3 inflammasome signaling and pyroptosis in cardiomyocytes. Mechanistically, coimmunoprecipitation assay showed that RBP4 interacted directly with NLRP3 in cardiomyocyte, while genetic knockdown or pharmacological inhibition of NLRP3 attenuated RBP4‐induced pyroptosis in cardiomyocytes. Finally, knockdown of RBP4 in heart decreased infarct size and protected against AMI‐induced pyroptosis and cardiac dysfunction in mice. Conclusions Taken together, these findings reveal RBP4 as a novel modulator promoting cardiomyocyte pyroptosis via interaction with NLRP3 in AMI. Therefore, targeting cardiac RBP4 might represent a viable strategy for the prevention of cardiac injury in patients with AMI.

Retinol binding protein 4 and its membrane receptors: a metabolic perspective

2015 ◽  
Vol 22 (1) ◽  
Author(s):  
Ronja Fedders ◽  
Matthias Muenzner ◽  
Michael Schupp
Keyword(s):  
Metabolic Diseases ◽  
Binding Protein ◽  
Current Data ◽  
Membrane Receptors ◽  
Retinol Binding Protein ◽  
Metabolic Effects ◽  
Retinol Binding Protein 4 ◽  
Underlying Mechanisms

AbstractNearly a decade of intense research has passed since the first report linking circulating retinol binding protein 4 (RBP4) to the development of insulin resistance. By now, a variety of underlying mechanisms have been identified; some of them are adherent to the canonical role of this circulating protein, which is to transport and deliver retinol to target tissues, and others that seem rather independent of retinol transport. Despite all these efforts, a consensus in the basic principles of RBP4’s metabolic effects has not been reached and some controversy remains. Using this as an opportunity, we here review and discuss current data on RBP4’s action on insulin sensitivity and its dependency on retinol homeostasis. We pay special attention to the involvement of RBP4 membrane receptors that were identified during these years, such as ‘stimulated by retinoic acid 6’ (STRA6), and whose identification added another layer of complexity to RBP4’s diverse actions. A better understanding of RBP4’s functions might allow its therapeutic exploitations, urgently needed in our period that is defined by an epidemic increase in metabolic diseases such as obesity and type 2 diabetes.

scholarly journals Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Chuyao Jin ◽  
Lizi Lin ◽  
Na Han ◽  
Zhiling Zhao ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Binding Protein ◽  
First Trimester ◽  
Retinol Binding Protein ◽  
Second Trimester ◽  
Retinol Binding Protein 4 ◽  
Plasma Retinol

Abstract Background To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM). Methods Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM. Results The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0 μg/L vs 14.4 μg/L; P < 0.05). Plasma RBP4 concentrations in the first and second trimester were associated with fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) in the second trimester (all P < 0.001). With adjustment for diet, physical activity, and other risk factors for GDM, the risk of GDM increased with every 1-log μg/L increment of RBP4 levels, and the OR (95% CI) was 3.12 (1.08–9.04) for RBP4 in the first trimester and 3.38 (1.03–11.08) for RBP4 in the second trimester. Conclusions Plasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.

Association of Retinol-Binding Protein 4 with Arteriovenous Fistula Dysfunction in Hemodialysis Patients

2021 ◽  
pp. 1-8
Author(s):  
Yuanhao Wu ◽  
Fan Wang ◽  
Tingting Wang ◽  
Yin Zheng ◽  
Li You ◽  
...  
Keyword(s):  
Risk Factor ◽  
Arteriovenous Fistula ◽  
Independent Risk Factor ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Youden Index ◽  
Serum Concentrations ◽  
Retinol Binding Protein 4 ◽  
Kaplan Meier ◽  
Increased Risk

<b><i>Background:</i></b> Arteriovenous fistula (AVF) is the most common vascular access for patients undergoing hemodialysis (HD). Neointimal hyperplasia (NIH) might be a potential mechanism of AVF dysfunction. Retinol-binding protein 4 (RBP4) may play an important role in the pathogenesis of NIH. The aim of this study was to investigate whether AVF dysfunction is associated with serum concentrations of RBP4 in HD subjects. <b><i>Methods:</i></b> A cohort of 65 Chinese patients undergoing maintenance HD was recruited between November 2017 and June 2019. The serum concentrations of RBP4 of each patient were measured with the ELISA method. Multivariate logistic regression was used to analyze data on demographics, biochemical parameters, and serum RBP4 level to predict AVF dysfunction events. The cutoff for serum RBP4 level was derived from the highest score obtained on the Youden index. Survival data were analyzed with the Cox proportional hazards regression analysis and Kaplan-Meier method. <b><i>Results:</i></b> Higher serum RBP4 level was observed in patients with AVF dysfunction compared to those without AVF dysfunction events (174.3 vs. 168.4 mg/L, <i>p</i> = 0.001). The prevalence of AVF dysfunction events was greatly higher among the high RBP4 group (37.5 vs. 4.88%, <i>p</i> = 0.001). In univariate analysis, serum RBP4 level was statistically significantly associated with the risk of AVF dysfunction (OR = 1.015, 95% CI 1.002–1.030, <i>p</i> = 0.030). In multivariate analysis, each 1.0 mg/L increase in RBP4 level was associated with a 1.023-fold-increased risk of AVF dysfunction (95% CI for OR: 1.002–1.045; <i>p</i> = 0.032). The Kaplan-Meier survival analysis indicated that the incidence of AVF dysfunction events in the high RBP4 group was significantly higher than that in the low-RBP4 group (<i>p</i> = 0.0007). Multivariate Cox regressions demonstrated that RBP4 was an independent risk factor for AVF dysfunction events in HD patients (HR = 1.015, 95% CI 1.001–1.028, <i>p</i> = 0.033). <b><i>Conclusions:</i></b> HD patients with higher serum RBP4 concentrations had a relevant higher incidence of arteriovenous dysfunction events. Serum RBP4 level was an independent risk factor for AVF dysfunction events in HD patients.

scholarly journals Retinol binding protein 4 (RBP4) concentration identifies V122I transthyretin cardiac amyloidosis

Amyloid ◽  
2017 ◽  
Vol 24 (sup1) ◽  
pp. 120-121 ◽  
Author(s):  
Marios Arvanitis ◽  
Steven Simon ◽  
Gloria Chan ◽  
Denise Fine ◽  
Paula Beardsley ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Retinol Binding Protein 4

Ontogenic expression pattern and genetic polymorphisms of the retinol-binding protein 4 (RBP4) gene in Erlang mountainous chickens

Gene ◽  
2013 ◽  
Vol 526 (2) ◽  
pp. 170-175 ◽  
Author(s):  
Hua-Dong Yin ◽  
Elizabeth R. Gilbert ◽  
Shi-Yi Chen ◽  
Di-Yan Li ◽  
Zhi-Chao Zhang ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Expression Pattern ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Retinol Binding Protein 4 ◽  
Ontogenic Expression ◽  
Rbp4 Gene

scholarly journals Serum Retinol-Binding Protein 4 (RBP4) and retinol in a cohort of borderline obese women with and without gestational diabetes

2010 ◽  
Vol 43 (3) ◽  
pp. 320-323 ◽  
Author(s):  
Beverly J. Tepper ◽  
Youn-Kyung Kim ◽  
Varsha Shete ◽  
Elena Shabrova ◽  
Loredana Quadro
Keyword(s):  
Gestational Diabetes ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Obese Women ◽  
Serum Retinol ◽  
Retinol Binding Protein 4
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