Microvascular Notch Signaling Is Upregulated in Response to Vascular Endothelial Growth Factor and Chronic Myocardial Ischemia
Microvascular Notch Signaling Is Upregulated in Response to Vascular Endothelial Growth Factor and Chronic Myocardial Ischemia
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DOI：
10.1253/circj.cj-13-0685
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发表时间：
2014-03-01
影响因子：
3.3
通讯作者：
Sellke, Frank W.
中科院分区：
文献类型：
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作者：
Lassaletta, Antonio D.;Elmadhun, Nassrene Y.;Sellke, Frank W.
背景：Notch信号是一种高度保守的促进血管和心肌生长的信号通路。假设外源性血管内皮生长因子（VEGF）管理缺血心肌将增强新生血管的反应和上调Notch信号进行了assessment.Methods和结果：14只雄性约克郡猪进行放置的ameroid收缩左回旋支动脉，以诱导慢性心肌缺血与一半的动物接受血管周围VEGF的缺血区域。远端区域作为正常心室对照（NV），而2个实验组由非VEGF动物的风险区域（AAR）和VEGF治疗动物的风险区域（VEGF）组成。VEGF组毛细血管和小动脉密度显著高于NV和AAR组。Notch受体和促新生血管Notch配体的表达在VEGF组中显著更高。锯齿状蛋白1和Notch 3是最高度集中在平滑肌壁的arterioles.Conclusions：VEGF管理慢性缺血心肌显着增加毛细血管和小动脉密度的新生血管反应，并导致上调的几个Notch受体和配体，这是不上调与缺血单独。这些发现表明，VEGF给药所观察到的增强的新生血管反应是通过VEGF诱导的Notch信号转导上调。
Background: Notch signaling is a highly conserved pathway that promotes vascular and myocardial growth. The hypothesis that exogenous vascular endothelial growth factor (VEGF) administration to ischemic myocardium would enhance the neovascular response and upregulate Notch signaling was assessed.Methods and Results: Fourteen male Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex artery to induce chronic myocardial ischemia with half of the animals receiving perivascular VEGF to the ischemic area. The remote territory served as the normal ventricle control (NV), while the 2 experimental groups consisted of the area at risk of the non-VEGF animals (AAR) and the area at risk of animals treated with VEGF (VEGF). Capillary and arteriolar density was significantly increased in the VEGF group as compared to both NV and AAR. Expression of Notch receptors and pro-neovascular Notch ligands was significantly higher in the VEGF group. Both Jagged 1 and Notch 3 were the most highly concentrated in the smooth muscle wall of arterioles.Conclusions: VEGF administration to chronically ischemic myocardium significantly augmented the neovascular response by an increase in both capillary and arteriolar density, and resulted in an upregulation of several Notch receptors and ligands, which were not upregulated with ischemia alone. These findings suggest that the augmented neovascular response seen with VEGF administration was through the VEGF-induced upregulation of Notch signaling.