Angiostatin is negatively associated with coronary collateral growth in patients with coronary artery disease
Angiostatin is negatively associated with coronary collateral growth in patients with coronary artery disease
复制标题
DOI：
10.1152/ajpheart.00669.2004
复制
发表时间：
2005-05-01
影响因子：
4.8
通讯作者：
March, K
中科院分区：
文献类型：
--
作者：
Matsunaga, T;Chilian, WM;March, K
血管抑制素是一种肿瘤血管生成抑制剂，由基质金属蛋白酶（MMP）作用于纤溶酶原产生。最近，我们报道了在冠状动脉侧枝生长和血管生成不足的模型中，血管抑制素水平升高，以应对缺血，尽管血管内皮生长因子（VEGF）水平很高。我们假设血管抑制素水平与患者侧支形成负相关。对37例接受冠状动脉搭桥手术的患者的冠状动脉造影进行评估，以确定血管造影上没有可见的侧支（Rentrop评分为0）或存在Rentrop分级3级（发育良好）的侧支。在旁路手术期间，从每位患者的心包液中提取，并对样本进行血管抑制素、纤溶酶原和VEGF的分析（Western分析），以及MMP-2和MMP-9的联合活性分析（酶谱分析）。无络组血管抑制素水平高于络发达组（3.1 +/- 0.2 vs 2.3 +/- 0.1光密度单位，P < 0.05）。两组患者的MMP活性和VEGF水平均无差异。与侧支血管发达的患者相比，无侧支血管的患者血管抑制素水平较高，反映了纤溶酶/纤溶酶原浓度较高（6.2 +/- 0.7比4.2 +/- 0.5光密度单位，P < 0.05）。我们的结果支持生长抑制剂血管抑制素可能对患者冠状动脉侧枝生长有负面影响的概念。也许试图刺激冠状动脉侧枝生长的治疗方法应该结合限制或中和生长抑制剂作用的方法。
Angiostatin, an inhibitor of tumor angiogenesis, is produced by the actions of matrix metalloproteinases (MMP) on plasminogen. Recently, we reported that angiostatin levels are increased in a model of inadequate coronary collateral growth and angiogenesis in response to ischemia, despite high levels of vascular endothelial growth factor (VEGF). We hypothesized that angiostatin levels are negatively associated with collateral formation in patients. Coronary angiograms from 37 patients undergoing coronary bypass surgery were evaluated for the absence of angiographically visible collaterals (Rentrop scores of 0) or the presence of Rentrop classification grade 3 (well developed) collaterals. Pericardial fluid was obtained from each patient during the bypass procedure, and the sample was analyzed for angiostatin, plasminogen, and VEGF ( Western analysis) and for combined activities of MMP-2 and MMP-9 (zymographic analysis). In patients with no collaterals, angiostatin level was greater compared with that in patients with well-developed collaterals (3.1 +/- 0.2 vs. 2.3 +/- 0.1 optical density units, P < 0.05). Neither MMP activities nor VEGF levels were different between the two groups of patients. The higher levels of angiostatin in patients with no visible collaterals were reflective of a higher concentration of plasmin/plasminogen (6.2 +/- 0.7 vs. 4.2 +/- 0.5 optical density units, P < 0.05) compared with those in patients with well-developed collateral vessels. Our results support the concept that the growth inhibitor angiostatin may have a negative impact on coronary collateral growth in patients. Perhaps therapies attempting to provoke coronary collateral growth should incorporate approaches to limit or neutralize the effects of growth inhibitors.