Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression
Abstract Angiogenesis plays a critical role in the progression and vulnerability of atherosclerotic plaques; however, the orchestration of angiogenesis in atherosclerotic plaque formation remains unclear. The results of microarray analysis, real-time PCR and immunohistochemical analyses showed that...
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2017
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oai:doaj.org-article:414b1bb3e3954d57b97c0645826d9aa82021-12-02T16:07:47ZHairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression10.1038/s41598-017-01018-62045-2322https://doaj.org/article/414b1bb3e3954d57b97c0645826d9aa82017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01018-6https://doaj.org/toc/2045-2322Abstract Angiogenesis plays a critical role in the progression and vulnerability of atherosclerotic plaques; however, the orchestration of angiogenesis in atherosclerotic plaque formation remains unclear. The results of microarray analysis, real-time PCR and immunohistochemical analyses showed that Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly decreased, while that of osteopontin (OPN) was increased, in atherosclerotic plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic plaques. The results of an in vitro study showed that Hes-1 was downregulated, while OPN was upregulated, in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1 knockdown was found to have transcriptional promotion effect on OPN expression in HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary, Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis in vitro and in vivo. The results of this study suggest that decreased Hes-1 expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN expression may be a promising strategy to prevent vulnerable plaque formation in patients with atherosclerosis.Xing-Xing YaoJing-Bo LuZhi-Dong YeLei ZhengQian WangZhi-Qi LinHao LiuHeng WanFang-Yong FuXian-Ying HuangJian-Chen XiuZheng-Jun LiuYan-Wei HuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q Xing-Xing Yao Jing-Bo Lu Zhi-Dong Ye Lei Zheng Qian Wang Zhi-Qi Lin Hao Liu Heng Wan Fang-Yong Fu Xian-Ying Huang Jian-Chen Xiu Zheng-Jun Liu Yan-Wei Hu Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression |
| description |
Abstract Angiogenesis plays a critical role in the progression and vulnerability of atherosclerotic plaques; however, the orchestration of angiogenesis in atherosclerotic plaque formation remains unclear. The results of microarray analysis, real-time PCR and immunohistochemical analyses showed that Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly decreased, while that of osteopontin (OPN) was increased, in atherosclerotic plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic plaques. The results of an in vitro study showed that Hes-1 was downregulated, while OPN was upregulated, in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1 knockdown was found to have transcriptional promotion effect on OPN expression in HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary, Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis in vitro and in vivo. The results of this study suggest that decreased Hes-1 expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN expression may be a promising strategy to prevent vulnerable plaque formation in patients with atherosclerosis. |
| format |
article |
| author |
Xing-Xing Yao Jing-Bo Lu Zhi-Dong Ye Lei Zheng Qian Wang Zhi-Qi Lin Hao Liu Heng Wan Fang-Yong Fu Xian-Ying Huang Jian-Chen Xiu Zheng-Jun Liu Yan-Wei Hu |
| author_facet |
Xing-Xing Yao Jing-Bo Lu Zhi-Dong Ye Lei Zheng Qian Wang Zhi-Qi Lin Hao Liu Heng Wan Fang-Yong Fu Xian-Ying Huang Jian-Chen Xiu Zheng-Jun Liu Yan-Wei Hu |
| author_sort |
Xing-Xing Yao |
| title |
Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression |
| title_short |
Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression |
| title_full |
Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression |
| title_fullStr |
Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression |
| title_full_unstemmed |
Hairy/enhancer of Split Homologue-1 Suppresses Vascular Endothelial Growth Factor-induced Angiogenesis via Downregulation of Osteopontin Expression |
| title_sort |
hairy/enhancer of split homologue-1 suppresses vascular endothelial growth factor-induced angiogenesis via downregulation of osteopontin expression |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/414b1bb3e3954d57b97c0645826d9aa8 |
| work_keys_str_mv |
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| _version_ |
1718384711893516288 |