Circulating FABP4 (Fatty Acid–Binding Protein 4) Is a Novel Prognostic Biomarker in Patients With Acute Ischemic Stroke

Tu, Wen‐Jun; Zeng, Xianwei; Deng, Aijun; Zhao, Shengjie; Luo, Ding-Zhen; Ma, Guo-Zhao; Wang, Hong; Liu, Qiang

doi:10.1161/strokeaha.117.017128

Cited by 70 publications

(41 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The lipid binding protein family consists of small (~15 kDa) soluble proteins that serve as modulators of intracellular lipid homeostasis by regulating long chain fatty acid transport in the nuclear and extra-nuclear cell compartments. The FABP4 isoform is predominantly expressed in adipose tissue, but also circulates in human plasma [73,74]. It is involved in intracellular lipid trafficking and has a role in the development of insulin resistance, atherosclerosis, and inflammatory processes.…”

Section: Alterations In Fatty Acids Metabolismmentioning

confidence: 99%

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

et al. 2019

View full text Add to dashboard Cite

Barth syndrome (BTHS) is an X-linked recessive multisystem disorder caused by mutations in the TAZ gene (TAZ, G 4.5, OMIM 300394) that encodes for the acyltransferase tafazzin. This protein is highly expressed in the heart and plays a significant role in cardiolipin biosynthesis. Heart disease is the major clinical manifestation of BTHS with a high incidence in early life. Although the genetic basis of BTHS and tetralinoleoyl cardiolipin deficiency in BTHS-affected individuals are well-established, downstream metabolic changes in cardiac metabolism are still uncovered. Our study aimed to characterize TAZ-induced metabolic perturbations in the heart. Control (PGP1-TAZWT) and TAZ mutant (PGP1-TAZ517delG) iPS-CM were incubated with 13C6-glucose and 13C5-glutamine and incorporation of 13C into downstream Krebs cycle intermediates was traced. Our data reveal that TAZ517delG induces accumulation of cellular long chain acylcarnitines and overexpression of fatty acid binding protein (FABP4). We also demonstrate that TAZ517delG induces metabolic alterations in pathways related to energy production as reflected by high glucose uptake, an increase in glycolytic lactate production and a decrease in palmitate uptake. Moreover, despite mitochondrial dysfunction, in the absence of glucose and fatty acids, TAZ517delG-iPS-CM can use glutamine as a carbon source to replenish the Krebs cycle.

show abstract

Section: Alterations In Fatty Acids Metabolismmentioning

confidence: 99%

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Functional outcome was assessed by the modified Rankin Scale (mRS) [16] blinded to serum biomarkers. A good functional outcome was defined as an mRS of 0-2 points, whereas a poor outcome was defined as an mRS of > 2 points [17]. Secondary end points were all-cause mortality within 6 months.…”

Section: Clinical Variables and Follow-upmentioning

confidence: 99%

Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke

Qiu

Cao

et al. 2018

Neurotherapeutics

Self Cite

View full text Add to dashboard Cite

Irisin was discovered as a PGC-1a-activated messenger of myocytes that links sedentary lifestyle, obesity, and diabetes. In this study, we investigated the short-term prognostic value of early measurement of irisin concentration in 1530 Han Chinese patients with acute ischemic stroke (AIS) from three stroke centers. The subjects were the first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Clinical information and stroke severity were collected at admission. Neurological evaluations were conducted at the 6-month follow-up. Serum levels of irisin, National Institutes of Health Stroke Scale (NIHSS), and conventional risk factors were evaluated to determine their value to predict functional outcome and mortality within 6 months. Multivariate analyses were performed using logistic regression models. During follow-up, a poor functional outcome was found in 588 patients (38.4%; 95% confidence interval (CI), 36.0-40.9%), and 325 patients died (21.2%; 95% CI, 19.2-23.3%). The stroke patients included in the study were divided into four groups according to irisin quartiles (first is the lowest level). Poor outcome across the irisin quartiles ranged from 54.5% (first quartile) to 21.7% (fourth quartile), and mortality rate ranged from 39.3% (first quartile) to 6.3% (fourth quartile). In a multivariate model using the first quartile (Q1) of irisin vs. Q2-Q4 together with the clinical variables, the marker displayed prognostic information and increased odds ratios of poor outcome by 58% (OR for Q1, 1.58 [95% CI, 1.12-2.43]) and mortality by 185% (OR for Q1, 2.85 [95% CI, 1.79-4.02]). In addition, a model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability to predict poor outcome (the area under the curve (AUC) with an increase from 0.73 to 0.75 [95% CI, 0.70-0.81]) and mortality (the AUC increased from 0.80 to 0.83 [95% CI, 0.78-0.87]). Irisin is a novel, independent prognostic marker improving currently used risk stratification of stroke patients. Further studies are needed to confirm this association, which may pave the way to new therapeutic options. Trial registration: ChiCTR-OPC- 17013501.

show abstract

“…The prognostic value of FABP4 in cardiovascular and cerebrovascular diseases was previously reported. Tu et al [24] showed that FABP4 was a novel independent prognostic marker in patients with ischemic stroke. FABP4 was also related to atherogenesis and poor outcome in acute ischemic stroke patients with carotid atherosclerosis [25].…”

Section: Discussionmentioning

confidence: 99%

The association between serum adipocyte fatty acid–binding protein and 3-month disability outcome after aneurysmal subarachnoid hemorrhage

Luo

Han

Sun

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: Adipocyte fatty acid-binding protein (FABP4) is an adipokine that plays an important role in development of cardiovascular and metabolic diseases. The aim of this study was to assess the 3-month prognostic value of serum levels of FABP4 in Chinese patients with aneurysmal subarachnoid hemorrhage (aSAH) on hospital admission. Methods: This was a prospective observational study from a stroke treatment center in Zhengzhou, China. From October 2016 to May 2018, patients with aSAH who were hospitalized within 24 h were included. In addition, 202 age-and gender-matched healthy volunteers were assigned to the healthy control group. At admission, serum levels of FABP4 were measured, and patients' characteristics, Hunt-Hess grade, and modified Fisher grade evaluated. At 3-month follow-up, functional outcome (Glasgow Outcome Scale score; dichotomized as poor [score 1-3] or good [score 4-5]) and all-cause mortality were recorded. Univariate and multivariate logistic regression models were used to investigate the association of FABP4 with the two endpoints. Results: A total of 418 patients with aSAH were included in this study. The median age was 58 years (interquartile range, 49-66 years), and 57.9% were women. FABP4 serum levels were related to Hunt-Hess score (r[Spearman] = 0.381; P < 0.001). Patients with a poor outcome and non-survivors had significantly increased serum FABP4 levels on admission (P < 0.001 for all). In multivariate logistic regression analysis, FABP4 was an independent predictor of poor outcome and mortality, with increased risks of 7% (odds ratios 1.07, 95% confidence interval [CI] 1.02-1.13; P = 0.001) and 5% (odds ratio 1.05, 95% CI, 1.01-1.12; P = 0.003), respectively. Receiver operating characteristics to predict functional outcome and mortality were significantly different between conventional risk factors (difference area under the curve 0.024, 95% CI 0.018-0.032) and FABP4 plus conventional risk factors (area under the curve 0.015, 95%CI 0.011-0.020). After FABP4 was added to the existing risk factors, mortality was better reclassified and was associated with the net reclassification improvement statistic (P = 0.009), while poor outcome was better reclassified and associated with both the integrated discrimination improvement and net reclassification improvement statistics (P < 0.05 for all). Conclusions: Elevated serum FABP4 levels were related to poor outcome and mortality in a cohort of patients with aSAH.

show abstract

Circulating FABP4 (Fatty Acid–Binding Protein 4) Is a Novel Prognostic Biomarker in Patients With Acute Ischemic Stroke

Abstract: Data show that FABP4 is a novel independent prognostic marker improving the currently used risk stratification of stroke patients.

Cited by 70 publications

References 35 publications

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Barth Syndrome: Exploring Cardiac Metabolism with Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke

The association between serum adipocyte fatty acid–binding protein and 3-month disability outcome after aneurysmal subarachnoid hemorrhage

Contact Info

Product

Resources

About