Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans.
Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans.
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DOI：
10.1007/s00125-011-2201-x
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发表时间：
2011-09
期刊：
影响因子：
8.2
通讯作者：
Mantzoros, C. S.
中科院分区：
文献类型：
--
作者：
Aronis, K. N.;Diakopoulos, K. N.;Fiorenza, C. G.;Chamberland, J. P.;Mantzoros, C. S.
在动物和体外研究中，瘦素已被证明通过上调几种促血管生成因子的产生来调节血管生成，但其在调节血管生成中的作用从未在人体中研究过。两个剂量的metreleptin（50和100 ng/ml）的潜在的血管生成作用进行了评估，在体外，使用一种新的三维血管生成测定。15名健康的正常瘦素血症志愿者在体内接受了生理（0.1 mg/kg）和药理（0.3 mg/kg）单剂量的metreleptin，两次不同的住院治疗间隔1-12周。注射metreleptin后0、6、12和24 h采集血清。将瘦素水平<5 ng/ml的20名瘦女性以1：1的方式随机接受生理替代剂量的metreleptin（0.04- 0.12mg/kg q.d.）或安慰剂治疗32周。在随机化后0、8、20和32周采集血清。进行蛋白质组血管生成阵列分析以筛选血管生成因子。还测量了血管生成素、血管生成素-1、血小板衍生内皮因子（PDGF）-AA、基质金属蛋白酶（MMP）8和9、内皮生长因子（EGF）和血管EGF（VEGF）的循环浓度。在体外模型中，两种metreleptin剂量均未能诱导血管生成。虽然短期和长期metreleptin管理的瘦素水平显着增加，血管生成标志物的循环浓度在体内没有显着变化。这是第一项研究，检查metreleptin管理在人类血管生成的影响。Metreleptin给药不调节人体内循环血管生成相关因子。
Leptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors, but its role in regulating angiogenesis has never been studied in humans. The potential angiogenic effect of two doses of metreleptin (50 and 100 ng/ml) was evaluated in vitro, using a novel three-dimensional angiogenesis assay. Fifteen healthy, normoleptinaemic volunteers were administered both a physiological (0.1 mg/kg) and a pharmacological (0.3 mg/kg) single dose of metreleptin, in vivo, on two different inpatient admissions separated by 1–12 weeks. Serum was collected at 0, 6, 12 and 24 h after metreleptin administration. Twenty lean women, with leptin levels <5 ng/ml, were randomised in a 1:1 fashion to receive either physiological replacement doses of metreleptin (0.04–0.12 mg/kg q.d.) or placebo for 32 weeks. Serum was collected at 0, 8, 20 and 32 weeks after randomisation. Proteomic angiogenesis array analysis was performed to screen for angiogenic factors. Circulating concentrations of angiogenin, angiopoietin-1, platelet derived endothelial factor (PDGF)-AA, matrix metalloproteinase (MMP) 8 and 9, endothelial growth factor (EGF) and vascular EGF (VEGF) were also measured. Both metreleptin doses failed to induce angiogenesis in the in vitro model. Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration, circulating concentrations of angiogenesis markers did not change significantly in vivo. This is the first study that examines the effect of metreleptin administration in angiogenesis in humans. Metreleptin administration does not regulate circulating angiogenesis related factors in humans.
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DOI：
10.1161/01.atv.0000256458.82320.be
发表时间：
2007-03-01
影响因子：
8.7
作者：
Kim, Kyung Eun;Cho, Chung-Hyun;Koh, Gou Young
通讯作者：
Koh, Gou Young
影响因子：
37.8
作者：
Moulton, KS;Heller, E;Folkman, J
通讯作者：
Folkman, J
影响因子：
13.5
作者：
Kitade, Mitsuteru;Yoshiji, Hitoshi;Fukui, Hiroshi
通讯作者：
Fukui, Hiroshi
影响因子：
20.1
作者：
Bouloumié, A;Drexler, HCA;Busse, R
通讯作者：
Busse, R
影响因子：
3.6
作者：
Brandon EL;Gu JW;Cantwell L;He Z;Wallace G;Hall JE
通讯作者：
Hall JE