血管内皮生长因子受体-2的丰富度增加,有助于血管内皮生长因子受体-1-缺乏的小鼠血管内皮生长的增加
Vivienne C Ho1, Li-Juan Duan, Chunxia Cronin
1Center for Vascular Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-3501, USA.
Circulation
|July 4, 2012
概括
血管内皮生长因子受体-1 (VEGFR-1) 缺乏通过增加VEGFR-2来增强血管形成 (血管生成). 这一发现为心血管疾病提供了新的治疗点.
科学领域:
- 心血管研究研究心血管研究
- 分子生物学分子生物学
- 血管新生的产生.
背景情况:
- 血管内皮生长因子受体-1 (VEGFR-1) 是心血管疾病的潜在治疗点.
- 它在血管生成中的确切作用是有争议的,从生殖线淘汰与基因酶域单独淘汰模型的结果是相互矛盾的.
研究的目的:
- 研究在成年小鼠中取消所有VEGFR-1功能域的发育,病理生理和分子后果.
- 阐明VEGFR-1在血管生成中的作用及其对心血管疾病模型的影响.
主要方法:
- 在新生儿和成年小鼠中,通过Cre-loxP介导的淘汰来消除VEGFR-1的所有功能域.
- 对发育,病理生理和分子结果的分析.
- 在心脏病发作后模型中评估血管生成,血管透性和信号通路 (VEGFR-2,Akt,ERK).
主要成果:
- 维格弗1缺乏促进了尖端细胞的形成,内皮细胞的增殖和功能性血管生成.
- 在心肌梗塞模型中,VEGFR-1 缺乏增强了血管生成,并提供了保护.
- VEGFR-1淘汰导致VEGFR-2的积累和信号增加,这可以通过向VEGFR-2或VEGF-A.部分逆转.
结论:
- 增加的VEGFR-2蛋白水平部分调解了在VEGFR-1缺乏小鼠中观察到的增强血管生成.
- 向VEGFR-2或VEGF-A可以调节血管生成在没有VEGFR-1的情况下.
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