血管内皮生长因子抑制同型半胱氨酸所致血管内皮细胞生长停滞的研究

VEGF Inhibits Homocysteine-induced Endothelial Cell Growth Arrest

目的:研究血管内皮生长因子(VEGF)对同型半胱氨酸所致血管内皮细胞生长停滞的作用及其分子机制。方法:用[3H]-胸腺嘧啶脱氧核苷掺入法测定细胞DNA合成率,基因表达测定采用RT-PCR。结果:①同型半胱氨酸诱导血管内皮细胞生长停滞、CHOP基因表达升高。VEGF能显著地抑制同型半胱氨酸诱导血管内皮细胞生长停滞,但不影响CHOP表达;②VEGF诱导核糖体蛋白RPS3a表达升高;③瞬时转染RPS3a基因抑制诱导血管内皮细胞生长停滞;④PI3K抑制剂wortmannin显著拮抗VEGF的作用,MEK抑制剂PD98059没有影响。结论:VEGF可通过PI3K信号途径上调RPS3a表达,抑制同型半胱氨酸诱导血管内皮细胞生长停滞,提示VEGF是一个潜在的抑制同型半胱氨酸所致动脉粥样硬化的药物。

Objective：To investigate the effect of vascular endothelial growth factor （VEGF） on cell growth arrest induced by homocysteine. Methods： DNA synthesis in cells was measured by using [^3 H]-thymidine incorporation. The expression of CHOP and ribosomal protein S3a （RPS3a） were detected by RT-PCR. Results： ① Homocysteine promoted cell growth arrest as well as expression of CHOP in endothelial cells. VEGF significantly inhibited homocysteine-induced endothelial cell growth arrest. However, VEGF did not affect homocysteine-induced CHOP expression. ② VEGF up-regulated the expression of RPS3a. ③ Transient transfection of RPS3a markedly suppressed homocysteine induced endothelial cell growth arrest. ④ PI3K inhibitor wortmannin,rather than MEK inhibitor PD98059, blocked the action of VEGF. Conclusion： The inhibitory effect of VEGF on homocysteine-induced endothelial cell growth arrest was due to its ability to elicit the expression of RPS3a through the PI3K pathway.