Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy.
Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy.
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DOI：
10.1161/circresaha.110.221317
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发表时间：
2010-08-20
影响因子：
20.1
通讯作者：
Smith LE
中科院分区：
文献类型：
--
作者：
Stahl A;Sapieha P;Connor KM;Sangiovanni JP;Chen J;Aderman CM;Willett KL;Krah NM;Dennison RJ;Seaward MR;Guerin KI;Hua J;Smith LE
欧米茄3长链多不饱和脂肪酸(ω3-PUFA)是一种强大的血管生成调节剂。然而，关于ω3-多不饱和脂肪酸依赖抑制血管生成的机制尚不清楚。本研究旨在确定ω3-PUFA抑制视网膜新生血管(NV)的主要机制。在氧源性视网膜病变小鼠模型的新生血管阶段单独应用ω3-PUFAs可诱导NV直接减少40%以上，而不改变血管闭塞(VO)或正常血管的再生。与过氧化物酶体增殖物激活受体(PPAR)抑制剂γ共同治疗几乎完全消除了这一作用。抑制PPARγ还可逆转ω3-PUFA诱导的视网膜肿瘤坏死因子α、细胞间黏附分子-1、血管细胞黏附分子-1、E-选择素和血管紧张素转换酶2的降低，但不能逆转血管内皮生长因子的作用。这些结果证实了PPARγ介导的ω3-PUFA对视网膜新生血管形成和视网膜血管生成激活的直接作用，这种作用不依赖于血管内皮生长因子。
Omega3 long-chain polyunsaturated fatty acids (ω3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing ω3-PUFA-dependent attenuation of angiogenesis. This study aims to identify a major mechanism by which ω3-PUFAs attenuate retinal neovascularization (NV). Administering ω3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy (OIR) induces a direct NV reduction of more than 40% without altering vaso-obliteration (VO) or the regrowth of normal vessels. Co-treatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR)γ almost completely abrogates this effect. Inhibition of PPARγ also reverses the ω3-PUFA-induced reduction of retinal TNFα, ICAM-1, VCAM-1, E-Selectin and Ang-2 but not VEGF. These results identify a direct, PPARγ-mediated effect of ω3-PUFAs on retinal NV formation and retinal angiogenic activation that is independent of VEGF.