Fatty acid-binding protein 4 is associated with endothelial dysfunction in patients with type 2 diabetes

Aragonès, Gemma; Ferré, Raimón; Lázaro, Iolanda; Cabré, Anna; Plana, Núria; Merino, Jordi; Heras, Mercedes; Girona, Josefa; Masana, Luís

doi:10.1016/j.atherosclerosis.2010.07.026

Cited by 57 publications

(43 citation statements)

References 15 publications

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“…A recent study demonstrated that FABP4 decreased the contractility of myocardial muscle cells, which suggests that the release of FABP4 into the bloodstream could have a direct effect on some peripheral cells and tissues[26]. In addition, we recently demonstrated that high levels of plasma FABP4, as well as other inflammation mediators, were associated with endothelial dysfunction as assessed by peripheral artery tonometry[27,28], and in an in vitro study, we previously demonstrated that recombinant FABP4 causes endothelial dysfunction by impairing the insulin-signalling pathway and NO production[29]. Furthermore, the elevated expression of intracellular FABP4 in endothelial cells was found to contribute to the dysfunction of these cells by reducing eNOS[30].…”

Section: Introductionmentioning

confidence: 99%

FABP4 Induces Vascular Smooth Muscle Cell Proliferation and Migration through a MAPK-Dependent Pathway

et al. 2013

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PurposeThe migration and proliferation of vascular smooth muscle cells play crucial roles in the development of atherosclerotic lesions. This study examined the effects of fatty acid binding protein 4 (FABP4), an adipokine that is associated with cardiovascular risk, endothelial dysfunction and proinflammatory effects, on the migration and proliferation of human coronary artery smooth muscle cells (HCASMCs). Methods and ResultsA DNA 5-bromo-2′-deoxy-uridine (BrdU) incorporation assay indicated that FABP4 significantly induced the dose-dependent proliferation of HCASMCs with a maximum stimulatory effect at 120 ng/ml (13% vs. unstimulated cells, p<0.05). An anti-FABP4 antibody (40 ng/ml) significantly inhibited the induced cell proliferation, demonstrating the specificity of the FABP4 proliferative effect. FABP4 significantly induced HCASMC migration in a dose-dependent manner with an initial effect at 60 ng/ml (12% vs. unstimulated cells, p<0.05). Time-course studies demonstrated that FABP4 significantly increased cell migration compared with unstimulated cells from 4 h (23%vs. 17%, p<0.05) to 12 h (74%vs. 59%, p<0.05). Pretreatment with LY-294002 (5 µM) and PD98059 (10 µM) blocked the FABP4-induced proliferation and migration of HCASMCs, suggesting the activation of a kinase pathway. On a molecular level, we observed an up-regulation of the MAPK pathway without activation of Akt. We found that FABP4 induced the active forms of the nuclear transcription factors c-jun and c-myc, which are regulated by MAPK cascades, and increased the expression of the downstream genes cyclin D1 and MMP2, CCL2, and fibulin 4 and 5, which are involved in cell cycle regulation and cell migration. ConclusionsThese findings indicate a direct effect of FABP4 on the migration and proliferation of HCASMCs, suggesting a role for this adipokine in vascular remodelling. Taken together, these results demonstrate that the FABP4-induced DNA synthesis and cell migration are mediated primarily through a MAPK-dependent pathway that activates the transcription factors c-jun and c-myc in HCASMCs.

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Section: Introductionmentioning

confidence: 99%

FABP4 Induces Vascular Smooth Muscle Cell Proliferation and Migration through a MAPK-Dependent Pathway

et al. 2013

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“…We demonstrated that induction of Fabp4 expression by rosiglitazone in the carotid artery was also RBP7 dependent. Previous studies suggest that high levels of plasma FABP4 are associated with endothelial dysfunction in patients with type 2 diabetes, which may be due in part to impaired insulin-mediated NO signaling in endothelium (48,49). It is uncertain if FABP4 serves a function similar to that of RBP7 in the endothelium, whether they carry similar ligands, or if they control distinct sets of PPARγ response genes.…”

Section: Discussionmentioning

confidence: 97%

Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin

Hu¹,

Keen²,

Lu³

et al. 2017

JCI Insight

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“…Our study also noted that female diabetic patients had higher A-FABP levels than man. In type 2 DM patients, A-FABP levels were positively correlated with BMI, TG, TCH, SBP, waist circumference, IL-6, TNF- α , and hs-CRP [23, 25]. Furthermore, A-FABP levels were positively correlated with plasma TG, apolipoprotein C-III, and all the components of TG-rich lipoproteins in type 2 diabetic subjects [26].…”

Section: Discussionmentioning

confidence: 99%

High Serum Adipocyte Fatty Acid Binding Protein Is Associated with Metabolic Syndrome in Patients with Type 2 Diabetes

Hou

et al. 2016

Journal of Diabetes Research

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Adipocyte fatty acid binding protein (A-FABP) is a key mediator of obesity-related metabolic syndrome (MetS). The aim of this study was to evaluate the relationship between A-FABP concentration and MetS in type 2 diabetes mellitus (DM) patients. Fasting blood samples were obtained from 165 type 2 DM volunteers. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Among 165 DM patients, 113 patients (68.5%) had MetS. Diabetic persons who had MetS had significantly higher A-FABP levels (P < 0.001) than those without MetS. Female DM persons had higher A-FABP level than man (P < 0.001). No statistically significant differences in A-FABP levels were found in use of statin, fibrate, or antidiabetic drugs. Multivariate forward stepwise linear regression analysis revealed that body fat mass (P < 0.001), logarithmically transformed creatinine (log-creatinine; P < 0.001), female DM patients (P < 0.001), and logarithmically transformed high sensitive C-reactive protein (log-hs-CRP; P = 0.013) were positively correlated, while albumin (P = 0.004) and glomerular filtration rate (GFR; P = 0.043) were negatively correlated with serum A-FABP levels in type 2 DM patients. In this study, higher serum A-FABP level was positively associated with MetS in type 2 DM patients.

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Fatty acid-binding protein 4 is associated with endothelial dysfunction in patients with type 2 diabetes

Cited by 57 publications

References 15 publications

FABP4 Induces Vascular Smooth Muscle Cell Proliferation and Migration through a MAPK-Dependent Pathway

FABP4 Induces Vascular Smooth Muscle Cell Proliferation and Migration through a MAPK-Dependent Pathway

Retinol-binding protein 7 is an endothelium-specific PPARγ cofactor mediating an antioxidant response through adiponectin

High Serum Adipocyte Fatty Acid Binding Protein Is Associated with Metabolic Syndrome in Patients with Type 2 Diabetes

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