Early increase in serum fatty acid binding protein 4 levels in patients with acute myocardial infarction

Obokata, Masaru; Iso, Tatsuya; Ohyama, Yoshiaki; Sunaga, Hiroaki; Kawaguchi, T; Matsui, Hiroki; Iizuka, Takashi; Fukuda, N; Takamatsu, Hiroto; Koitabashi, Norimichi; Funada, Ryuichi; Takama, Noriaki; Kasama, Shu; Kaneko, Yoshiaki; Yokoyama, Tetsuji; Murakami, Masami; Kurabayashi, Masahiko

doi:10.1177/2048872616683635

Cited by 21 publications

(30 citation statements)

References 41 publications

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“…The coronary veno-arterial difference in FABP4 levels in the aortic root and coronary sinus was shown to be an independent predictor of the severity of coronary stenosis after adjustment of conventional risk factors 35) . FABP4 levels are significantly elevated during the early hours after onset of acute myocardial infarction and are robustly increased in out-of-hospital cardiac arrest survivors, probably due to rapid lipolytic release of FABP4 from epicardial fat by adrenergic overdrive that accompanies acute cardiovascular disease 104) .…”

Section: Circulating Fabp4 Levelmentioning

confidence: 99%

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

Furuhashi

2019

J Atheroscler Thromb

197

177

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The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Review Fatty acid-binding proteins (FABPs), a family of lipid chaperones, contribute to systemic metabolic regulation via several lipid signaling pathways. Fatty acid-binding protein 4 (FABP4), known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays important roles in the development of insulin resistance and atherosclerosis in relation to metabolically driven low-grade and chronic inflammation, referred to as 'metaflammation'. FABP4 is secreted from adipocytes in a non-classical pathway associated with lipolysis and acts as an adipokine for the development of insulin resistance and atherosclerosis. Circulating FABP4 levels are associated with several aspects of metabolic syndrome and cardiovascular disease. Ectopic expression and function of FABP4 in cells and tissues are also related to the pathogenesis of several diseases. Pharmacological modification of FABP4 function by specific inhibitors, neutralizing antibodies or antagonists of unidentified receptors would be novel therapeutic strategies for several diseases, including obesity, diabetes mellitus, atherosclerosis and cardiovascular disease. Significant roles of FABP4 as a lipid chaperone in physiological and pathophysiological conditions and the possibility of FABP4 being a therapeutic target for metabolic and cardiovascular diseases are discussed in this review. Fatty Acid-Binding Proteins (FABPs) Fatty acid trafficking in cells affects many aspects of cellular function 3). Fatty acids act both as an energy source and as signals for metabolic regulations including gene expression, inflammatory and metabolic responses, and growth and survival pathways. Fatty acid-binding proteins (FABPs), a family of intracellular lipid chaperones, regulate lipid trafficking and responses in cells and are linked to metabolic and inflammatory pathways 3-6). FABPs are abundantly expressed 14-15-kDa proteins that reversibly bind hydrophobic ligands, such as long-chain fatty acids and other lipids. It has been proposed that FABPs actively facilitate the transport of fatty acids to specific organelles in the cell for lipid oxidation in the mitochondrion or peroxisome, transcriptional regulation in the nucleus, signaling, trafficking and membrane synthesis in the endoplasmic reticulum (ER), and regula-Copyright©2019 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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Section: Circulating Fabp4 Levelmentioning

confidence: 99%

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

Furuhashi

2019

J Atheroscler Thromb

197

177

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“…Without serial testing of FABP4 levels, we yielded no data regarding the change of FABP4 levels in those nondiabetic stroke patients. Interestingly, one study reported significantly elevated FABP4 levels during the early hours after the occurrence of acute myocardial infarction [51]. In addition, cerebrospinal fluid samples were not obtained.…”

Section: Discussionmentioning

confidence: 99%

Serum fatty acid binding protein 4 is positively associated with early stroke recurrence in nondiabetic ischemic stroke

Jiang

et al. 2019

Aging

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Adipocyte fatty acid–binding protein (FABP4) played critical roles in metabolic syndrome, inflammatory responses and cardiovascular diseases. It aimed to investigate the associations of serum FABP4 levels with early stroke recurrence. This study included the 206 acute ischemic stroke patients hospitalized in our institution. Stroke recurrence events were assessed at the 3-month follow-up. The median of FABP level was 22.6 (IQR, 17.9-31.6) ng/mL in patients with stroke recurrence (N=36), which was higher than in patients without stroke recurrence [16.9 (IQR, 11.8-21.4) ng/mL] (P<0.001). As a continuous variable, the unadjusted and adjusted risk of stroke recurrence would be increased by 12% (OR=1.12 [95% CI 1.06–1.17], P<0.001) and 8% (1.08 [1.02–1.14], P=0.006) for every 1 ng/ml increment of FABP4. The Area under the curve (AUC) of serum FABP4 and NIH Stroke Scale (NIHSS) score for predicting stroke recurrence was 0.73 (95% CI: 0.64–0.82) and 0.72 (95% CI: 0.64–0.81), presenting no discriminating capacity (P=0.45). In the combining model, the AUC of NIHSS score was further improved to 0.77 by FABP4 (0.77; 95% CI: 0.69–0.85), which was significant (P=0.01). The risk of stroke recurrence can be predicted by elevated FABP4 levels in serum of nondiabetic patients with first-ever ischemic stroke.

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“…On the other hand, elevation of circulating FABP4 occurs when GFR is markedly reduced or abolished. Circulating FABP4 is negatively correlated with GFR and markedly increased up to 20-fold in patients undergoing maintenance hemodialysis 8 , 10 – 12 . We showed that BLN induced marked elevation of circulating FABP4.…”

Section: Discussionmentioning

confidence: 99%

“…FABP4 is secreted from adipocytes despite the lack of an N-terminal secretory signal sequence via ER-Golgi-independent pathways 5 – 7 . Secretion of FABP4 is enhanced by lipolysis, which is accelerated during fasting and activation of sympathetic nervous system in a β-adrenergic receptors-dependent manner 5 , 6 , 8 , 9 . On the other hand, FABP4 is likely to be eliminated from the circulation mainly by renal clearance 10 – 12 .…”

Section: Introductionmentioning

confidence: 99%

Circulating FABP4 is eliminated by the kidney via glomerular filtration followed by megalin-mediated reabsorption

Shrestha

Sunaga

Hanaoka

et al. 2018

Sci Rep

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Circulating fatty acid binding protein 4 (FABP4), secreted from adipocytes, is a potential biomarker for metabolic and cardiovascular diseases. Circulating FABP4 levels are positively associated with adiposity and adrenergic stimulation, but negatively with renal function. In this study, we addressed the issue of how the kidney regulates clearance of circulating FABP4. Tracing study revealed remarkable accumulation of 125I-labeled FABP4 in the kidney. Exogenous FABP4 was exclusively detected in the apical membrane of proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in marked elevation of circulating FABP4 levels. Accelerated lipolysis by β-3 adrenergic stimulation led to a marked elevation in circulating FABP4 in mice with severe renal dysfunction. Megalin, an endocytic receptor expressed in PTECs, plays a major role in reabsorption of proteins filtered through glomeruli. Quartz-crystal microbalance study revealed that FABP4 binds to megalin. In kidney-specific megalin knockout mice, a large amount of FABP4 was excreted in urine while circulating FABP4 levels were significantly reduced. Our data suggest that circulating FABP4 is processed by the kidney via the glomerular filtration followed by megalin-mediated reabsorption. Thus, it is likely that circulating FABP4 levels are determined mainly by balance between secretion rate of FABP4 from adipocytes and clearance rate of the kidney.

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Early increase in serum fatty acid binding protein 4 levels in patients with acute myocardial infarction

Cited by 21 publications

References 41 publications

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

Serum fatty acid binding protein 4 is positively associated with early stroke recurrence in nondiabetic ischemic stroke

Circulating FABP4 is eliminated by the kidney via glomerular filtration followed by megalin-mediated reabsorption

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