Miyazawa-Hoshimoto S, Takahashi K, Bujo H, Hashimoto N, Saito Y
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Japan.
Diabetologia. 2003 Nov;46(11):1483-8. doi: 10.1007/s00125-003-1221-6. Epub 2003 Oct 8.
AIMS/HYPOTHESIS: Adipose tissue expresses some bioactive molecules, which may be involved in the development of obesity-associated metabolic disorders and cardiovascular diseases. Vascular endothelial growth factor (VEGF) an important angiogenic factor is implicated in normal and pathological vessel formation. The aim of this study is to investigate clinically the association between blood serum VEGF concentrations and body fat accumulation as well as distribution. The study also aims to show the effect of serum VEGF protein on gene expression of transcriptional factor E26 transformation-specific-1 (Ets-1) and matrix metalloproteinase (MMP)-3.
Serum VEGF concentrations were measured in 38 overweight or obese subjects. Fat distribution in the abdominal subcutaneous as well as visceral fat areas was assessed by computed tomography scans at umbilical level. Furthermore, the changes of serum VEGF concentrations following body weight reduction therapy were analyzed in eight subjects recruited from the original pool of subjects. Semi-purified circulating VEGF proteins were obtained by heparin-sepharose and its biological activities were shown to alter gene expressions in human aortic endothelial cells.
Serum VEGF concentrations were positively correlated with BMI (r=0.433, p=0.007) and visceral fat area (r=0.488, p=0.002). Stepwise regression analysis showed the visceral fat area as the most important determinant factor for VEGF circulating levels. Following body weight reduction therapy, VEGF concentrations as well as visceral fat area were decreased. The serum semi-purified VEGF protein enhanced expressions of Ets-1 and MMP-3 in human aortic endothelial cells.
CONCLUSION/INTERPRETATION: Increased serum VEGF concentrations associated with visceral fat accumulation could influence vascular endothelial function.
目的/假设：脂肪组织表达一些生物活性分子，这些分子可能参与肥胖相关代谢紊乱和心血管疾病的发生发展。血管内皮生长因子（VEGF）作为一种重要的血管生成因子，与正常和病理性血管形成有关。本研究旨在临床调查血清VEGF浓度与体脂积累及分布之间的关联。该研究还旨在展示血清VEGF蛋白对转录因子E26转化特异性-1（Ets-1）和基质金属蛋白酶（MMP）-3基因表达的影响。
测量了38名超重或肥胖受试者的血清VEGF浓度。通过脐水平的计算机断层扫描评估腹部皮下及内脏脂肪区域的脂肪分布。此外，对从原始受试者群体中招募的8名受试者进行体重减轻治疗后血清VEGF浓度的变化进行了分析。通过肝素-琼脂糖获得半纯化的循环VEGF蛋白，并显示其生物学活性可改变人主动脉内皮细胞中的基因表达。
血清VEGF浓度与BMI呈正相关（r = 0.433，p = 0.007），与内脏脂肪面积呈正相关（r = 0.488，p = 0.002）。逐步回归分析显示内脏脂肪面积是VEGF循环水平的最重要决定因素。体重减轻治疗后，VEGF浓度以及内脏脂肪面积均降低。血清半纯化VEGF蛋白增强了人主动脉内皮细胞中Ets-1和MMP-3的表达。
结论/解读：与内脏脂肪积累相关的血清VEGF浓度升高可能影响血管内皮功能。
