Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload
Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload
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DOI：
10.1161/01.hyp.0000215207.54689.31
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发表时间：
2006-05-01
期刊：
影响因子：
8.3
通讯作者：
Walsh, K
中科院分区：
文献类型：
--
作者：
Izumiya, Y;Shiojima, I;Walsh, K
心肌肥厚与心肌中血管内皮生长因子(VEGF)表达上调有关。在这里，我们评估了诱骗的血管内皮生长因子受体对压力超负荷肥厚小鼠心脏形态和功能的影响。给小鼠注射携带诱饵血管内皮生长因子受体的重组腺病毒载体(Ad-Flk)，利用横动脉缩窄(TAC)造成心脏压力超负荷。使用Ad-Flk治疗可使接受TAC治疗的心脏中的毛细血管密度净减少。Ad-Flk还可减轻TAC诱导的心肌肥厚，促进左心室扩张和收缩功能的丧失。Ad-Flk治疗后心肌纤维化明显增加，胶原基因表达明显上调。相比之下，在假手术组小鼠中，Ad-Flk对这些参数中的任何一个都没有影响。给予血管内皮生长因子诱导剂可减轻压力超负荷的心肌肥厚，促进心力衰竭的进展，但对假手术组动物无影响。这些发现表明，血管内皮生长因子是维持心肌毛细血管密度所必需的，血管床的减少与从代偿性肥厚到衰竭的转变有关。
Cardiac hypertrophy is associated with upregulation of vascular endothelial growth factor ( VEGF) in the myocardium. Here, we evaluated the effects of a decoy VEGF receptor on heart morphology and function to a murine model of pressure overload hypertrophy. Mice were administered adenoviral vector encoding a decoy VEGF receptor (Ad-Flk), and their hearts were subjected to pressure overload by transverse aortic constriction (TAC). Treatment with Ad-Flk led to a net reduction in capillary density in hearts subjected to TAC. Ad-Flk also led to a reduction in TAC-induced cardiac hypertrophy and promoted left ventricle dilatation and a loss in contractile function. Treatment with Ad-Flk markedly increased myocardial fibrosis and collagen gene upregulation. In contrast, Ad-Flk had no effect on any of these parameters in sham-treated mice. Administration of a VEGF trap reagent diminished pressure overload cardiac hypertrophy and promoted the progression to heart failure but had no effect on sham-treated animals. These findings suggest that VEGF is required to maintain myocardial capillary density and that reductions in the vascular bed are associated with the transition from compensatory hypertrophy to failure.