7-Ketocholesterol induces inflammation and angiogenesis in vivo: a novel rat model.
7-Ketocholesterol induces inflammation and angiogenesis in vivo: a novel rat model.
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DOI：
10.1371/journal.pone.0056099
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rodríguez IR
中科院分区：
文献类型：
--
作者：
Amaral J;Lee JW;Chou J;Campos MM;Rodríguez IR
脂质沉积物中7-酮胆固醇（7KCh）的积累与多种慢性疾病有关，包括动脉粥样硬化、阿尔茨海默病和年龄相关性黄斑变性。已知7KCh对各种类型的培养细胞具有促炎和细胞毒性，但对其在体内的作用知之甚少。在本研究中，我们通过在大鼠眼前房植入可生物降解晶片来研究7KCh在体内的作用。晶圆是用两种可生物降解聚合物和不同量的7KCh的混合物制备的。含有7kch的植入物诱导大量血管生成和炎症。相比之下，含胆固醇的植入物没有血管生成，也几乎没有炎症。荧光素血管造影监测新生血管的生长情况。植入后4天观察到新生血管，7 ~ 10天达到高峰。血管造影和分离素IB4标记显示新生血管起源于角膜缘，并通过角膜生长。抗cd68免疫标记表明含7kch的植入物有广泛的巨噬细胞浸润以及其他细胞类型。通过荧光免疫标记和房水（AH）免疫印迹也观察到含7kch植入物中VEGF的显著增加。直接测量VEGF， IL-1β和GRO/KC显示这些因子在7kch -植入物的AH中显著升高。总之，本研究证明了两个重要的事实：1)7KCh在体内具有促血管生成和促炎症的作用；2)含有7KCh的植入物可用于大鼠血管生成模型。
Accumulation of 7-Ketocholesterol (7KCh) in lipid deposits has been implicated in a variety of chronic diseases including atherosclerosis, Alzheimer's disease and age-related macular degeneration. 7KCh is known to be pro-inflammatory and cytotoxic to various types of cultured cells but little is known about its effects in vivo. In this study we have investigated the effects of 7KCh in vivo by implanting biodegradable wafers into the anterior chamber of the rat eye. The wafers were prepared using a mixture of two biodegradable polymers with different amounts of 7KCh. The 7KCh-containing implants induced massive angiogenesis and inflammation. By contrast, no angiogenesis and very little inflammation were observed with cholesterol-containing implants. The neovessel growth was monitored by fluorescein angiography. Neovessels were observed 4 days post implantation and peaked between 7 to 10 days. The angiography and isolectin IB4 labeling demonstrated that the neovessels originated from the limbus and grew through the cornea. Immunolabeling with anti-CD68 suggested that the 7KCh-containing implants had extensive macrophage infiltration as well as other cell types. A significant increase in VEGF was also observed in 7KCh-containing implants by fluorescent immunolabeling and by immunoblot of the aqueous humor (AH). Direct measurement of VEGF, IL-1β and GRO/KC demonstrated a marked elevation of these factors in the AH of the 7KCh-implants. In summary this study demonstrates two important things: 1) 7KCh is pro-angiogenic and pro–inflammatory in vivo and 2) implants containing 7KCh may be used to create a novel angiogenesis model in rats.
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DOI：
10.1016/j.bbalip.2012.01.013
发表时间：
2012-04
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Huang JD;Amaral J;Lee JW;Larrayoz IM;Rodriguez IR
通讯作者：
Rodriguez IR
影响因子：
5.5
作者：
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通讯作者：
Richmond, A
DOI：
10.1007/s11746-010-1572-3
发表时间：
2010-09
期刊：
Journal of the American Oil Chemists' Society
影响因子：
--
作者：
Busch TP;King AJ
通讯作者：
King AJ
DOI：
10.1136/bjophthalmol-2011-300344
发表时间：
2011-12
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Curcio CA;Johnson M;Rudolf M;Huang JD
通讯作者：
Huang JD
影响因子：
5
作者：
Dugas, B.;Charbonnier, S.;Lizard, Gerard
通讯作者：
Lizard, Gerard