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子痫前期患者母血中的脂联素多聚体

Maternal serum adiponectin multimers in preeclampsia.

作者信息

Mazaki-Tovi Shali, Romero Roberto, Vaisbuch Edi, Kusanovic Juan Pedro, Erez Offer, Gotsch Francesca, Chaiworapongsa Tinnakorn, Than Nandor Gabor, Kim Sun Kwon, Nhan-Chang Chia-Ling, Jodicke Cristiano, Pacora Percy, Yeo Lami, Dong Zhong, Yoon Bo Hyun, Hassan Sonia S, Mittal Pooja

机构信息

Perinatology Research Branch, Intramural Division, NICHD/NIH/DHHS, Hutzel Women's Hospital, Bethesda, MD, USA.

出版信息

J Perinat Med. 2009;37(4):349-63. doi: 10.1515/JPM.2009.085.

Abstract

OBJECTIVE

Obesity, insulin resistance, and dyslipidemia are associated with preeclampsia. Recently, "adipose tissue failure", characterized by dysregulation of adipokine production, has been implicated in the pathophysiology of these metabolic complications. Adiponectin, an insulin-sensitizing, anti-atherogenic, anti-inflammatory and angiogenic adipokine, circulates in oligomeric complexes including: low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms. These multimers exert differential biological effects, and HMW to total adiponectin ratio (S(A)) has been reported to be a specific marker of adiponectin activity. The aim of this study was to determine whether preeclampsia is associated with changes in circulating adiponectin multimers.

STUDY DESIGN

This cross-sectional study included women with: 1) normal pregnancy (n=225); and 2) patients with mild preeclampsia (n=111). The study population was further stratified by first trimester BMI (normal weight <25 kg/m(2) vs. overweight/obese >or=25 kg/m(2)). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Non-parametric statistics were used for analysis.

RESULTS

  1. The median maternal HMW and LMW adiponectin concentrations were lower in patients with preeclampsia than in those with normal pregnancies (P<0.001 and P=0.01, respectively); 2) patients with preeclampsia had a lower HMW/total adiponectin ratio (P<0.001) and higher MMW/total adiponectin and LMW/total adiponectin ratios than those with a normal pregnancy (P<0.001 and P=0.009, respectively); 3) the presence of preeclampsia was independently associated with lower maternal serum HMW adiponectin concentrations (P=0.001) and with a low HMW/total adiponectin ratio (P<0.001) after correction for maternal age, maternal BMI, the difference in BMI between the third and the first trimester, and gestational age at sampling; and 4) overweight/obese pregnant women had a lower median total and HMW adiponectin concentration than normal weight pregnant women among women with normal pregnancies, but not among those with preeclampsia.

CONCLUSION

  1. Preeclampsia is associated with a lower median concentration of the HMW adiponectin isoform, the most active form of this adipokine, and a low HMW/total adiponectin ratio, a specific marker of adiponectin biologic activity; 2) in contrast to normal pregnancy, preeclampsia is not associated with decreased circulating adiponectin multimers in overweight/obese individuals suggesting altered regulation of this adipokine in preeclampsia; 3) collectively, these findings suggest that preeclampsia is characterized by alterations in adiponectin multimers and their relative distribution implying a role for adiponectin multimers in the mechanism of disease in preeclampsia.
摘要

目的

肥胖、胰岛素抵抗和血脂异常与子痫前期相关。最近,以脂肪因子产生失调为特征的“脂肪组织功能衰竭”被认为与这些代谢并发症的病理生理学有关。脂联素是一种具有胰岛素增敏、抗动脉粥样硬化、抗炎和促血管生成作用的脂肪因子,以寡聚复合物的形式循环,包括:低分子量(LMW)三聚体、中分子量(MMW)六聚体和高分子量(HMW)异构体。这些多聚体发挥不同的生物学作用,据报道,HMW与总脂联素的比值(S(A))是脂联素活性的一个特异性标志物。本研究的目的是确定子痫前期是否与循环脂联素多聚体的变化有关。

研究设计

这项横断面研究纳入了以下女性:1)正常妊娠者(n = 225);2)轻度子痫前期患者(n = 111)。研究人群根据孕早期体重指数进一步分层(正常体重<25 kg/m² 与超重/肥胖≥25 kg/m²)。采用酶联免疫吸附测定法(ELISA)测定血清脂联素多聚体(总、HMW、MMW和LMW)浓度。使用非参数统计进行分析。

结果

1)子痫前期患者母体HMW和LMW脂联素浓度中位数低于正常妊娠者(分别为P<0.001和P = 0.01);2)子痫前期患者的HMW/总脂联素比值较低(P<0.001),MMW/总脂联素和LMW/总脂联素比值高于正常妊娠者(分别为P<0.001和P = 0.009);3)在校正母体年龄、母体体重指数、孕晚期与孕早期体重指数差值以及采样时的孕周后,子痫前期的存在与母体血清HMW脂联素浓度较低(P = 0.001)以及低HMW/总脂联素比值(P<0.001)独立相关;4)在正常妊娠女性中,超重/肥胖孕妇的总脂联素和HMW脂联素浓度中位数低于正常体重孕妇,但子痫前期患者中并非如此。

结论

1)子痫前期与HMW脂联素异构体(该脂肪因子最具活性的形式)的浓度中位数较低以及HMW/总脂联素比值较低有关,HMW/总脂联素比值是脂联素生物学活性的一个特异性标志物;2)与正常妊娠不同,子痫前期与超重/肥胖个体中循环脂联素多聚体减少无关,这表明子痫前期中该脂肪因子的调节发生了改变;3)总体而言,这些发现表明子痫前期的特征是脂联素多聚体及其相对分布的改变,这意味着脂联素多聚体在子痫前期疾病机制中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a06/3166229/3d8023f1aefe/nihms304929f1.jpg

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