Increased plasma retinol binding protein 4 levels in patients with inflammatory cardiomyopathy

Increased plasma retinol binding protein 4 levels in patients with inflammatory cardiomyopathy
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DOI:
10.1093/eurjhf/hfp153
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发表时间:
2009-12-01
影响因子:
18.2
通讯作者:
Skurk, Carsten
Skurk, Carsten
中科院分区:
医学1区
文献类型:
--
作者:
Bobbert, Peter;Weithaeuser, Alice;Skurk, Carsten

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慢性心力衰竭(CHF)与糖尿病的高风险相关。视黄醇结合蛋白4 (RBP 4)是一种脂肪组织来源的蛋白,具有促糖尿病作用。对CHF和胰岛素抵抗之间关系的完整理解仍然难以捉摸。本研究旨在探讨CHF与糖尿病的关系。在扩张型心肌病(DCM, n = 53)、扩张型炎症性心肌病(DCMi, n = 54)和对照组(n = 20)患者中,评估RBP 4、胰岛素和白细胞介素(IL) 2、8和10的血浆水平。此外,我们还在体外脂肪细胞中探讨了RBP 4调控的可能机制。采用特异性ELISA法测定血浆RBP 4和胰岛素水平。多重ELISA法测定白细胞介素浓度。用3T3-L1脂肪细胞进行细胞培养,检测IL-8刺激后RBP - 4mrna的表达。与DCM组(35.54 +/- 23.08 mu g/mL)和对照组(27.3 +/- 18.51 mu g/mL)相比,DCMi组RBP 4水平显著升高(52.95 +/- 20.42 mu g/mL)。DCMi患者血浆RBP 4与IL-8呈正相关(r=0.416, P < 0.05)。此外,与对照组和DCM组相比,DCMi患者的胰岛素抵抗增加。在体外,IL-8诱导脂肪细胞RBP 4mrna表达显著上调。IL-8诱导的RBP - 4血浆浓度升高可能是导致DCMi患者糖尿病发病率升高的机制之一。
Chronic heart failure (CHF) is associated with a higher risk for diabetes mellitus. Retinol binding protein 4 (RBP 4) is an adipose tissue-derived protein with pro-diabetogenic effects. A complete understanding of the association of CHF and insulin resistance remains elusive. The purpose of this study was to examine the relationship between CHF and diabetes mellitus.Plasma levels of RBP 4, insulin, and interleukins (IL) 2, 8, and 10, were assessed in patients with dilated cardiomyopathy (DCM, n = 53), dilated inflammatory cardiomyopathy (DCMi, n = 54), and controls (n = 20). In addition, a possible mechanism of RBP 4 regulation was examined in adipocytes in vitro. Plasma levels of RBP 4 and insulin were measured by a specific ELISA. Interleukin concentrations were obtained by multiplex ELISA. Cell culture with 3T3-L1 adipocytes was performed to measure RBP 4 mRNA expression after stimulation with IL-8. RBP 4 levels were significantly increased in patients with DCMi (52.95 +/- 20.42 mu g/mL) compared with DCM (35.54 +/- 23.08 mu g/mL) and the control group (27.3 +/- 18.51 mu g/mL). RBP 4 was positively correlated with IL-8 (r=0.416, P < 0.05) in human plasma in patients with DCMi. Moreover, increased insulin resistance was observed in patients with DCMi compared with the control and DCM groups. In vitro, IL-8 induced a significant upregulation of RBP 4 mRNA expression in adipocytes.Elevated RBP 4 plasma concentrations, induced by IL-8, might be one mechanism leading to a higher incidence of diabetes in patients with DCMi.