Quantitative Analysis of Factors Regulating Angiogenesis for Stem Cell Therapy

干细胞治疗中血管生成调控因素的定量分析

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作者:Takahiro Shimazaki, Nobuhiro Noro, Kazuhiro Hagikura, Taro Matsumoto, Chikako Yoshida-Noro

Background

The control of angiogenesis is essential in disease treatment. We investigated angiogenesis-promoting or -suppressing factors and their molecular mechanisms. (2)

Conclusions

We showed the promoting effect of Ang-1 or DFAT and the suppressing effect of polyphenols on angiogenesis and studied their molecular mechanisms. These results help control angiogenesis in regenerative therapy.

Methods

Angiogenesis from HUVECs was quantitatively analyzed using the Angiogenesis Analysis Kit (Kurabo, Osaka, Japan). Human rAng-1-producing 107-35 CHO cells or mouse DFAT-D1 cells were co-cultured with HUVEC. Antioxidant polyphenols were added to the culture. Gene expression was analyzed by RT-PCR. (3)

Results

The addition of rAng-1-producing cells, their culture supernatant, or commercially available rAng-1 showed a promoting effect on angiogenesis. The co-culture of DFAT-D1 cells promoted angiogenesis. Polyphenols showed a dose-dependent inhibitory effect on angiogenesis. Luteolin and quercetin showed remarkable anti-angiogenic effects. The expression of vWF, Flk1, and PECAM-1 was increased by adding rAng-1-producing cell culture supernatant. Polyphenols suppressed these genes. Apigenin and luteolin markedly suppressed α-SMA and Flk1. Resveratrol and quercetin enhanced the expression of PPARγ, and luteolin suppressed the expression of COX-1. The expression of endothelial nitric oxide synthase (eNOS), an oxidative stress-related gene, was slightly increased by luteolin. These results suggest that polyphenols induce ROS reduction. (4) Conclusions: We showed the promoting effect of Ang-1 or DFAT and the suppressing effect of polyphenols on angiogenesis and studied their molecular mechanisms. These results help control angiogenesis in regenerative therapy.

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