High cholesterol feeding in C57/Blc6 mice alters expression within the VEGF receptor-ligand family in corporal tissue.
High cholesterol feeding in C57/Blc6 mice alters expression within the VEGF receptor-ligand family in corporal tissue.
复制标题
C57/Blc6 小鼠的高胆固醇喂养会改变体内组织中 VEGF 受体配体家族的表达。
DOI：
10.1111/j.1743-6109.2008.00801.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Annex,BrianH
中科院分区：
文献类型：
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作者：
Xie,Donghua;Hazarika,Surovi;Andrich,AmyJ;Padgett,MikeE;Kontos,ChristopherD;Donatucci,CraigF;Annex,BrianH
血管生成是指血管在现有血管结构中的生长和增殖，由多种细胞因子和受体介导，其中最重要的是血管内皮生长因子(VEGF)家族。目的血管内皮生长因子受体信号的降低与小体组织血管反应性的异常有关，但目前尚不清楚血管内皮生长因子配体和/或受体的改变是否参与了这一过程。主要观察指标我们试图确定C57BL6小鼠在胆固醇喂养时血管反应性及血管内皮生长因子配体和受体家族表达的变化。方法24只小鼠(N=8只/组)分别饲喂正常饲料(第1组)或1.25%高胆固醇饲料4(第2组)或12周(第3组)。在体条上进行等长张力研究，并绘制剂量反应曲线，以评估内皮依赖性和非内皮依赖性血管反应性。用聚合酶链式反应和/或免疫印迹/酶联免疫吸附试验检测血管内皮生长因子-A、B、C、D、血管内皮生长因子受体(VEGFRs)水平。结果术后4周内皮依赖性血管反应性略有下降，但差异有统计学意义。与1组相比，2组VEGFR-1的mRNA和蛋白水平均降低，而VEGF-B水平升高，而血管内皮细胞含量和血管内皮细胞含量无明显变化。12周时，血管内皮依赖性和非内皮依赖性血管反应性均明显降低，大多数血管内皮生长因子配体(除血管内皮生长因子B外)、受体和受体信号均减少。结论C57BL6小鼠喂饲胆固醇可导致血管内皮生长因子受体-配体家族的改变，这种改变最初可能有助于限制血管损伤的程度，但随着胆固醇喂养的持续，这些适应作用就失效了。
IntroductionAngiogenesis, the growth and proliferation of blood vessels from existing vascular structures, is mediated by many cytokine growth factors and receptors, among the most important are the vascular endothelial growth factor (VEGF) family.AimDecreases in VEGF receptor signaling have been linked to abnormalities in vasoreactivity in corporal tissue, but it is unknown if alterations in the VEGF ligands and/or receptors contribute to this process.Main Outcome MeasuresWe sought to determine changes in vasoreactivity and the expression of the family of VEGF ligands and receptors in corporal tissue with cholesterol feeding in C57BL6 mice.MethodsTwenty-four mice (N = 8/group) were fed a normal diet (Group 1) or a 1.25% high cholesterol diet for 4 (Group 2) or 12 (Group 3) weeks. Isometric tension studies were performed on corporal strips and dose response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivities. Levels of VEGF-A, B, C, D, VEGF receptors (VEGFRs) were detected by PCR (polymerase chain reaction) and/or western blot/enzyme-linked immunosorbent assay (ELISA). Endothelial and smooth muscle cell contents were determined by immunohistochemistry.ResultsAt 4 weeks there was a small but significant decrease in endothelium-dependent vasoreactivity. Both mRNA and protein levels of VEGFR-1 were decreased, while VEGF-B was increased in Group 2 vs. Group 1, with no change in VEGF-A or endothelial cell content. By 12 weeks, decreases in both endothelium-dependent and endothelium-independent vasoreactivity were evident with decrease in most VEGF ligands (except VEGF-B), receptors, and receptor signaling.ConclusionsCholesterol feeding in C57BL6 mice results in alterations in the VEGF receptor-ligand family that may initially serve to limit the degree of vascular injury but these adaptations fail with the continuation of cholesterol feeding.