VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis
VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis
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DOI：
10.1152/ajpheart.1996.270.5.h1803
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发表时间：
1996-05-01
影响因子：
4.8
通讯作者：
Simons, M
中科院分区：
文献类型：
--
作者：
Li, J;Brown, LF;Simons, M
血管内皮生长因子 (VEGF) 是一种内皮细胞有丝分裂原，被认为通过与两种高亲和力受体 flk-1 和 flt-1 相互作用而发挥作用。在成人心脏中，血管生成可发生在多种病理状况下，包括动脉粥样硬化、肥大和梗塞。为了确定 VEGF、flk-1 和 flt-1 在体内这一过程中发挥的作用，我们研究了大鼠梗塞模型中生长因子及其受体的表达。急性心肌梗死后，我们观察到整个心脏中 VEGF (275%)、flk-1 (375%) 和 flt-1 (400%) mRNA 表达最初快速（1 小时）上升。最初左心室中 VEGF、flk-1 和 flt-1 表达的弥漫性诱导后来被主要局限于发生血管生成的心肌梗死区域的增加所取代。原位杂交显示，梗塞后6小时，梗塞区附近的活肌细胞表达的VEGF量显着增加。在 6 小时和 24 小时，梗塞边缘的微血管均过表达 flk-1 和 flt-1 mRNA；在第3天和第7天，浸润梗塞部位的新血管也过度表达这两种受体，并持续长达6周。总之，急性心肌梗死伴随着VEGF及其受体表达的快速、持久增加，具有特征性的空间和时间动力学。这些发现表明 VEGF/VEGF 受体系统在与心肌梗塞相关的血管生成和基质沉积中发挥重要作用。
Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that is thought to function by interacting with two high-affinity receptors, flk-1 and flt-1. In an adult heart, angiogenesis can occur in a number of pathological conditions, including atherosclerosis, hypertrophy, and infarction. To determine the role played by VEGF, flk-1, and flt-1 in this process in vivo, we studied the expression of the growth factor and its receptors in a rat infarct model. After an acute myocardial infarction, we observed an initial rapid (1 h) rise in VEGF (275%), flk-1 (375%), and flt-1 (400%) mRNA expression throughout the entire heart. Initial diffuse induction of VEGF, flk-1, and flt-1 expression in the left ventricle was later replaced by an increase predominantly limited to perimyocardial infarction areas where angiogenesis was taking place. In situ hybridization showed at 6 h after infarction, viable myocytes adjacent to the infarct zone expressed markedly increased amounts of VEGF. At both 6 and 24 h, microvessels at the infarct edge overexpressed both flk-1 and flt-1 mRNAs; at 3 and 7 days new vessels infiltrating the infarct also overexpressed both receptors and continued for as late as 6 wk. In summary, acute myocardial infarction is accompanied by rapid and prolonged increase in expression of VEGF and its receptors with characteristic spatial and temporal kinetic. These findings suggest that the VEGF/VEGF receptor system plays an important role in the angiogenesis and stromal deposition associated with myocardial infarction.