Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication

Furuhashi, Masato; Yuda, Satoshi; Muranaka, Atsuko; Kawamukai, Mina; Matsumoto, Megumi; Tanaka, Marenao; Moniwa, Norihito; Ohnishi, Hirofumi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

doi:10.1253/circj.cj-17-1295

Cited by 34 publications

(31 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ApoE-deficient mice and in the human microvascular endothelium, previous work shows that A-FABP has an independent role in atherogenesis; additionally, enhanced expression of A-FABP was associated with reduced expression of eNOS and nitric oxide (NO) production [19,23]. Additional work showed an association between serum A-FABP levels and endothelial dysfunction [24,25,26]. Furuhashi et al reported that serum levels of A-FABP correlated positively with changes in carotid intima-media thickness in subjects without medications [25].…”

Section: Discussionmentioning

confidence: 99%

“…Additional work showed an association between serum A-FABP levels and endothelial dysfunction [24,25,26]. Furuhashi et al reported that serum levels of A-FABP correlated positively with changes in carotid intima-media thickness in subjects without medications [25]. Aragones et al demonstrated that circulating A-FABP levels were associated with endothelial dysfunction as measured by reactive hyperemia index in DM patients [24].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Serum Adipocyte Fatty Acid-Binding Protein Level is Negatively Associated with Vascular Reactivity Index Measured by Digital Thermal Monitoring in Kidney Transplant Patients

Chen

Lee

et al. 2019

Metabolites

View full text Add to dashboard Cite

Adipocyte fatty acid-binding protein (A-FABP) is abundantly found in mature adipocytes and is involved in cardiovascular disease. Our aim is to investigate the association between serum A-FABP levels and endothelial function among kidney transplant (KT) patients. Fasting blood samples were obtained from 80 KT patients. Serum A-FABP levels were measured using a commercially available enzyme immunoassay kit. Endothelial function and vascular reactivity index (VRI) were measured using digital thermal monitoring test. In this study, VRI < 1.0, VRI 1.0–1.9, and VRI ≥ 2.0 were defined as poor, intermediate, and good vascular reactivity, respectively. There were 12 (15.0%), 30 (37.5%), and 38 (47.5%) KT patients categorized as having poor, intermediate, and good vascular reactivity, respectively. Increased serum levels of alkaline phosphatase (p = 0.012), γ-glutamyltranspeptidase (GGT; p = 0.032), and A-FABP (p < 0.001) were associated with decreased vascular reactivity. Multivariable forward stepwise linear regression analysis revealed that age (β = −0.283, adjusted R2 change = 0.072; p = 0.003) and serum log-A-FABP level (β = −0.514, adjusted R2 change = 0.268; p < 0.001) were significantly associated with VRI values in KT patients. We concluded that serum fasting A-FABP level is negatively associated with VRI values and plays a role in endothelial dysfunction of KT patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum Adipocyte Fatty Acid-Binding Protein Level is Negatively Associated with Vascular Reactivity Index Measured by Digital Thermal Monitoring in Kidney Transplant Patients

Chen

Lee

et al. 2019

Metabolites

View full text Add to dashboard Cite

show abstract

“…Circulating FABP4 is independently associated with the level of PCSK9, which binds to and degrades the low-density lipoprotein (LDL) receptor, suggesting associations with hypercholesterolemia and cardiovascular risk 95) . Furthermore, the basal FABP4 level is independently associated with change in carotid intima-media thickness, a marker of atherosclerosis, per year, indicating that FABP4 level predicts progress of atherosclerosis 96) . It has also been reported that serum FABP4 level predicts long-term cardiovascular events and mortality 82, 97–99) .…”

Section: Circulating Fabp4 Levelmentioning

confidence: 99%

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

Furuhashi

2019

J Atheroscler Thromb

Self Cite

209

177

View full text Add to dashboard Cite

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.

show abstract

“…Lipolysis-associated secretion of FABP4 from adipocytes is caused by a non-classical secretion pathway (7,11) despite the lack of signal peptides (1), and secreted FABP4 has effects as an adipokine on insulin resistance, atherosclerosis and vascular remodeling (7,8,12). An elevation of FABP4 concentration is associated with metabolic disorders and cardiovascular events (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). It has recently been shown that FABP4 concentration is modulated by several therapeutic drugs for diabetes mellitus, dyslipidemia and hypertension (24)(25)(26)(27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

et al. 2020

Self Cite

View full text Add to dashboard Cite

Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus. Methods: As a sub-analysis study of the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial, 256 patients (male/female: 146/110, age: 68 ± 10 years) with type 2 diabetes mellitus and dyslipidemia who were receiving statin therapy were recruited. Patients who had been treated with a thiazolidinedione were excluded. Results: Several drugs which may modulate FABP4 levels including statins, dipeptidyl peptidase-4 inhibitors and angiotensin II receptor blockers had been administered in 100, 81, and 51% of the recruited patients, respectively. The level of FABP4, but not that of FABP5, was significantly higher in females than in males. Multivariable linear regression analysis demonstrated that waist circumference (β = 0.21), estimated glomerular filtration rate (β = −0.31), triglycerides (β = 0.16), and FABP5 (β = 0.39) were independent predictors of FABP4 level after adjusting age and sex. On the other hand, FABP5 level was independently associated with levels of FABP4 (β = 0.57) and high-density lipoprotein (HDL) cholesterol (β = −0.12). Conclusions: Concentrations of FABP4 and FABP5 are independent predictors of each other in patients with type 2 diabetes mellitus. There are distinct independent associations of FABP4 with renal dysfunction, adiposity and hypertriglyceridemia and there is a distinct independent association of FABP5 with a low HDL cholesterol level in type 2 diabetic patients with dyslipidemia at high risks for cardiovascular disease who are receiving statin therapy.

show abstract

Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication

Cited by 34 publications

References 40 publications

Serum Adipocyte Fatty Acid-Binding Protein Level is Negatively Associated with Vascular Reactivity Index Measured by Digital Thermal Monitoring in Kidney Transplant Patients

Serum Adipocyte Fatty Acid-Binding Protein Level is Negatively Associated with Vascular Reactivity Index Measured by Digital Thermal Monitoring in Kidney Transplant Patients

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus

Contact Info

Product

Resources

About