Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness

Bobbert, Thomas; Raila, Jens; Schwärz, F.; Mai, Knut; Henze, Andrea; Pfeiffer, Andreas F. H.; Schweigert, Florian J.; Spranger, Joachim

doi:10.1016/j.atherosclerosis.2010.07.063

Cited by 83 publications

(67 citation statements)

References 10 publications

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“…The proinflammatory effects of RBP4 on macrophages are mediated in part through activation of toll-like receptor 4 (TLR4) and c-Jun N-terminal protein kinase (JNK) signaling and are retinol independent, since apo-RBP4 (retinol free) and holo-RBP4 (retinol bound) have the same proinflammatory effects (53). The finding that RBP4 stimulates proinflammatory pathways in macrophages, combined with previous studies that found that serum RBP4 levels correlate significantly with the presence of subclinical inflammation (5), hypertension (58), stroke (34,57), atherosclerosis (10,58), and diabetic retinopathy (43,60), suggests that elevation of serum RBP4 may contribute to vascular disease by inducing endothelial inflammation; however, the effect of RBP4 on endothelial inflammation has not been studied.…”

supporting

confidence: 52%

“…Clinical studies have linked elevation of serum RBP4 to vascular inflammation and vascular disease (10,34,43,57,58,60). However, the significance of RBP4 elevation in the pathogenesis of vascular disease is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Since elevation of serum RBP4 has been linked to insulin resistance in type 2 diabetes (25,32,68) as well as in microvascular and macrovascular diseases (10,34,43,57,58,60), it is important to determine how RBP4 affects both subtypes of endothelial cells. To establish if RBP4 exerts similar proinflammatory effects in macrovascular endothelial cells, we analyzed the effects of RBP4 on the expression of proinflammatory molecules and the activation of NF-B and NADPH oxidase in human umbilical vein endothelial cells (HUVEC).…”

Section: Rbp4-induced Endothelial Inflammation Occurs In Huvec Via Nfmentioning

confidence: 99%

“…Thus, understanding the factors that contribute to the development and progression of cardiovascular disease and microvascular complications is necessary to prolong survival and improve quality of life for patients with type 2 diabetes. Recent clinical studies have linked elevated serum RBP4 specifically to cardiovascular disease, including hypertension (58), stroke (34,57), and atherosclerosis (10,58). In addition, two studies have reported that patients with proliferative diabetic retinopathy, which is characterized by destructive retinal neovascularization and vision loss, have a significantly pronounced elevation of RBP4 compared to patients with mild or no retinopathy (43,60).…”

mentioning

confidence: 99%

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Retinol-Binding Protein 4 Induces Inflammation in Human Endothelial Cells by an NADPH Oxidase- and Nuclear Factor Kappa B-Dependent and Retinol-Independent Mechanism

Farjo

Farjo²,

Halsey

et al. 2012

Molecular and Cellular Biology

131

113

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b Serum retinol-binding protein 4 (RBP4) is the sole specific vitamin A (retinol) transporter in blood. Elevation of serum RBP4 in patients has been linked to cardiovascular disease and diabetic retinopathy. However, the significance of RBP4 elevation in the pathogenesis of these vascular diseases is unknown. Here we show that RBP4 induces inflammation in primary human retinal capillary endothelial cells (HRCEC) and human umbilical vein endothelial cells (HUVEC) by stimulating expression of proinflammatory molecules involved in leukocyte recruitment and adherence to endothelium, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). We demonstrate that these novel effects of RBP4 are independent of retinol and the RBP4 membrane receptor STRA6 and occur in part via activation of NADPH oxidase and NF-B. Importantly, retinol-free RBP4 (apo-RBP4) was as potent as retinol-bound RBP4 (holo-RBP4) in inducing proinflammatory molecules in both HRCEC and HUVEC. These studies reveal that RBP4 elevation can directly contribute to endothelial inflammation and therefore may play a causative role in the development or progression of vascular inflammation during cardiovascular disease and microvascular complications of diabetes.

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supporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Rbp4-induced Endothelial Inflammation Occurs In Huvec Via Nfmentioning

confidence: 99%

mentioning

confidence: 99%

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Retinol-Binding Protein 4 Induces Inflammation in Human Endothelial Cells by an NADPH Oxidase- and Nuclear Factor Kappa B-Dependent and Retinol-Independent Mechanism

Farjo

Farjo²,

Halsey

et al. 2012

Molecular and Cellular Biology

131

113

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“…It is suggested that RBP4 is a predictor of atherosclerosis and its clinical manifestations -cardiovascular diseases. Circulating RBP4 levels are positively associated with intima media thickness, an established parameter of atherosclerosis (55). Increased RBP4 levels are found in subjects with cerebral infarction, associated with earlier cardiovascular disease, and increased risk of incident coronary disease (56)(57)(58).…”

Section: Rbp4 In Insulin Resistance and T2d: Clinical Studiesmentioning

confidence: 91%

RBP4: a controversial adipokine

Kotnik

Fischer‐Posovszky

Wabitsch

2011

European Journal of Endocrinology

208

158

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Adipose tissue is an endocrine organ secreting biologically active factors called adipokines that act on both local and distant tissues. Adipokines have an important role in the development of obesity-related comorbidities not only in adults but also in children and adolescents. Retinol binding protein 4 (RBP4) is a recently identified adipokine suggested to link obesity with its comorbidities, especially insulin resistance, type 2 diabetes (T2D), and certain components of the metabolic syndrome. However, data, especially resulting from the clinical studies, are conflicting. In this review, we summarize up-to-date knowledge on RBP4's role in obesity, development of insulin resistance, and T2D. Special attention is given to studies on children and adolescents. We also discuss the role of possible confounding factors that should be taken into account when critically evaluating published studies or planning new studies on this exciting adipokine.

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Associations of RBP4 with lipid metabolism and renal function in diabetes mellitus

Wang

Song

et al. 2013

Euro J Lipid Sci & Tech

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To investigate the plasma retinol-binding protein 4 (RBP4), small dense low-density lipoprotein cholesterol (sdLDL-C), oxidized low-density lipoprotein (ox-LDL) levels and to evaluate the associations of RBP4 with abnormal lipid metabolism and renal dysfunction in type 2 diabetes mellitus (T2DM) patients, we determined RBP4, sdLDL-C, ox-LDL levels and renal parameters in 120 T2DM patients with or without nephropathy and 70 controls. The correlation analysis and multiple linear regression analysis were performed. Compared with controls, the RBP4 and sdLDL-C levels were found significantly increased only in diabetic nephropathy (DN) patients and ox-LDL levels were elevated in both groups of T2DM patients. The RBP4 levels were positively correlated with sdLDL-C, ox-LDL, and negatively with estimated glomerular filtration rate (eGFR) in all the T2DM patients. Multiple linear regression analysis showed that sdLDL-C and eGFR were the independent predictors of RBP4 levels, and RBP4 were one of the independent determinants for sdLDL-C and ox-LDL levels in T2DM patients, respectively. In conclusion, plasma RBP4, sdLDL-C, ox-LDL levels were significantly increased in DN patients. Circulating RBP4 may be associated with abnormal lipid metabolism and renal dysfunction, and considered as a biomarker of cardiovascular disease and renal function in T2DM patients. Practical applications:The findings in the present study support the hypothesis that circulating RBP4 not only plays an important role in lipid metabolism abnormalities of atherosclerosis, contributing to the increased risk of CVD, but also could reflect renal dysfunction and be associated with the severity of nephropathy in T2DM patients. Therefore, the clinical monitoring of plasma RBP4 level as well as its dynamic changes may possess distinctly clinical value for assessments of renal function and CVD risk in T2DM patients. These findings may contribute to the further understanding of the pathogenic role of circulating RBP4 in proatherogenic dyslipidemia and nephropathy in T2DM.

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Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness

Cited by 83 publications

References 10 publications

Retinol-Binding Protein 4 Induces Inflammation in Human Endothelial Cells by an NADPH Oxidase- and Nuclear Factor Kappa B-Dependent and Retinol-Independent Mechanism

Retinol-Binding Protein 4 Induces Inflammation in Human Endothelial Cells by an NADPH Oxidase- and Nuclear Factor Kappa B-Dependent and Retinol-Independent Mechanism

RBP4: a controversial adipokine

Associations of RBP4 with lipid metabolism and renal function in diabetes mellitus

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