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 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.

• Authors: 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
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 898 (04 18 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28420872 (Publication Type: Journal Article)

Chemical References

• Transcription Factor HES-1
• Vascular Endothelial Growth Factor A
• Osteopontin
• HES1 protein, human

Topics

• Adult
• Aged
• Animals
• Chick Embryo
• Down-Regulation
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Male
• Middle Aged
• Neovascularization, Physiologic
• Osteopontin (genetics, metabolism)
• Plaque, Atherosclerotic (metabolism)
• Transcription Factor HES-1 (genetics, metabolism)
• Vascular Endothelial Growth Factor A (pharmacology)