Isomers of conjugated linoleic acid differ in their effects on angiogenesis and survival of mouse mammary adipose vasculature
Isomers of conjugated linoleic acid differ in their effects on angiogenesis and survival of mouse mammary adipose vasculature
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DOI：
10.1093/jn/134.2.299
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发表时间：
2004-02-01
影响因子：
4.2
通讯作者：
Ip, MM
中科院分区：
文献类型：
--
作者：
Masso-Welch, PA;Zangani, D;Ip, MM
膳食共轭亚油酸（CLA）是一种癌症化学预防剂，已被证明可以抑制体内和体外血管生成，并降低小鼠乳腺中血管内皮生长因子（VEGF）和Flk-1的浓度。为了确定哪种异构体介导CLA在体内的抗血管生成作用，在CD 2F 1Cr小鼠中比较了补充有5或10 g/kg c9，t11 -或t10，c12-CLA异构体的饮食的作用。两种异构体均抑制体内基质胶颗粒的功能性血管形成，并降低血清VEGF浓度; t10，c12异构体还降低促血管生成激素瘦素（P < 0.05）。此外，t10，c12异构体，而不是c9，t11-CLA，迅速诱导白色和棕色脂肪细胞以及乳房脂肪垫的预先存在的支持血管的凋亡（P < 0.05）。独立于这种异构体特异性脂肪细胞凋亡效应，两种异构体均诱导单室脂肪细胞直径快速且可逆的减小（P < 0.05）。两种CLA异构体在体内抑制血管生成的能力可能有助于它们抑制致癌作用的能力。此外，我们建议，每个共轭亚油酸异构体独特的修改乳腺基质的“土壤”的方式，是有用的化学预防乳腺癌。
Dietary conjugated linoleic acid (CLA) is a cancer chemopreventive agent that has been shown to inhibit angiogenesis in vivo and in vitro, and to decrease vascular endothelial growth factor (VEGF) and Flk-1 concentrations in the mouse mammary gland. To determine which isomer mediates the antiangiogenic effects of CLA in vivo, the effects of diets supplemented with 5 or 10 g/kg c9,t11 - or t10,c12-CLA isomers were compared in CD2F1Cr mice. Both isomers inhibited functional vascularization of a matrigel pellet in vivo and decreased serum VEGF concentrations; the t10,c12 isomer also decreased the proangiogenic hormone leptin (P < 0.05). Additionally, the t10,c12 isomer, but not c9,t11-CLA, rapidly induced apoptosis of the white and brown adipocytes as well as the preexisting supporting vasculature of the mammary fat pad (P < 0.05). Independent of this isomer-specific adipose apoptotic effect, both isomers induced a rapid and reversible decrease in the diameter of the unilocular adipocytes (P < 0.05). The ability of both CLA isomers to inhibit angiogenesis in vivo may contribute to their ability to inhibit carcinogenesis. Moreover, we propose that each CLA isomer uniquely modifies the mammary stromal "soil" in a manner that is useful for chemoprevention of breast cancer.