IGFBP‐4 enhances VEGF‐induced angiogenesis in a mouse model of myocardial infarction
IGFBP‐4 enhances VEGF‐induced angiogenesis in a mouse model of myocardial infarction
复制标题
IGFBP-4 增强心肌梗死小鼠模型中 VEGF- 诱导的血管生成
DOI：
10.1111/jcmm.15516
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发表时间：
2020
影响因子：
5.3
通讯作者：
Dan‐ni Ren
中科院分区：
文献类型：
--
作者：
Da Wo;Jinxiao Chen;Qiongyu Li;En Ma;Hongwei Yan;Jun Peng;Weidong Zhu;Yong Fang;Dan‐ni Ren
血管内皮生长因子（VEGF）是一种众所周知的血管生成因子，然而其促进心肌梗死（MI）后治疗性血管生成的能力有限。在这里，我们的目的是研究胰岛素样生长因子结合蛋白- 4 （IGFBP - 4）的双重治疗是否可以有效地提高心肌梗死后VEGF的治疗效果。与IGFBP - 4联合治疗可以增强VEGF诱导的血管生成，并通过提高关键血管生成因子血管生成素- 1的表达来防止细胞损伤。两种药物的双重治疗可协同降低心肌梗死后的心肌纤维化标志物胶原- I和胶原- III。重要的是，IGFBP - 4的保护作用发生在缺血损伤的早期，而VEGF的作用发生在较晚的血管生成阶段。我们的研究结果表明，VEGF单独治疗往往不足以保护氧化应激和促进缺血后血管生成，而IGFBP4和VEGF联合治疗可以利用这些药物的双重作用有效地保护缺血和氧化损伤，并促进血管生成。这些发现为这些药物在临床中的作用提供了重要的见解，并提出了治疗缺血性心脏病的新策略。
Vascular endothelial growth factor (VEGF) is a well‐known angiogenic factor, however its ability in promoting therapeutic angiogenesis following myocardial infarction (MI) is limited. Here, we aimed to investigate whether dual treatment with insulin‐like growth factor binding protein‐4 (IGFBP‐4), an agent that protects against early oxidative damage, can be effective in enhancing the therapeutic effect of VEGF following MI. Combined treatment with IGFBP‐4 enhanced VEGF‐induced angiogenesis and prevented cell damage via enhancing the expression of a key angiogenic factor angiopoietin‐1. Dual treatment with the two agents synergistically decreased cardiac fibrosis markers collagen‐I and collagen‐III following MI. Importantly, while the protective action of IGFBP‐4 occurs at an early stage of ischemic injury, the action of VEGF occurs at a later stage, at the onset angiogenesis. Our findings demonstrate that VEGF treatment alone is often not enough to protect against oxidative stress and promote post‐ischemic angiogenesis, whereas the combined treatment with IGFBP4 and VEGF can utilize the dual roles of these agents to effectively protect against ischemic and oxidative injury, and promote angiogenesis. These findings provide important insights into the roles of these agents in the clinical setting, and suggest new strategies in the treatment of ischemic heart disease.