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Vascular Biology

Intermedin

A Novel Regulator for Vascular Remodeling and Tumor Vessel Normalization by Regulating Vascular Endothelial-Cadherin and Extracellular Signal–Regulated Kinase

Wei Zhang, Li-Jun Wang, Fei Xiao, Yi Wei, Wei Ke, Hong-Bo Xin
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https://doi.org/10.1161/ATVBAHA.112.300185
Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.300185
Originally published August 23, 2012
Wei Zhang
From the Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China (W.Z., L-J.W., W.K., H-B.X); West China Second Hospital, Sichuan University, Chengdu, China (F.X.); and Laboratory of Cardiovascular Diseases, Institute of Translational Medicine, Nanchang University, Nanchang, China (Y.W., H-B.X).
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Li-Jun Wang
From the Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China (W.Z., L-J.W., W.K., H-B.X); West China Second Hospital, Sichuan University, Chengdu, China (F.X.); and Laboratory of Cardiovascular Diseases, Institute of Translational Medicine, Nanchang University, Nanchang, China (Y.W., H-B.X).
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Fei Xiao
From the Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China (W.Z., L-J.W., W.K., H-B.X); West China Second Hospital, Sichuan University, Chengdu, China (F.X.); and Laboratory of Cardiovascular Diseases, Institute of Translational Medicine, Nanchang University, Nanchang, China (Y.W., H-B.X).
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Yi Wei
From the Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China (W.Z., L-J.W., W.K., H-B.X); West China Second Hospital, Sichuan University, Chengdu, China (F.X.); and Laboratory of Cardiovascular Diseases, Institute of Translational Medicine, Nanchang University, Nanchang, China (Y.W., H-B.X).
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Wei Ke
From the Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China (W.Z., L-J.W., W.K., H-B.X); West China Second Hospital, Sichuan University, Chengdu, China (F.X.); and Laboratory of Cardiovascular Diseases, Institute of Translational Medicine, Nanchang University, Nanchang, China (Y.W., H-B.X).
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Hong-Bo Xin
From the Molecular Medicine Research Center, West China Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China (W.Z., L-J.W., W.K., H-B.X); West China Second Hospital, Sichuan University, Chengdu, China (F.X.); and Laboratory of Cardiovascular Diseases, Institute of Translational Medicine, Nanchang University, Nanchang, China (Y.W., H-B.X).
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Abstract

Objective—Intermedin (IMD), a member of calcitonin family, was suggested to play a role in angiogenesis and cancer. The aim of this study was to investigate the role of IMD in the angiogenic process and the underlying mechanism, and the possibility for it to be used as a target for angiogenesis-based anticancer therapies.

Methods and Results—Using in vivo and in vitro 3-dimensional angiogenic models, we found that IMD induced a well-ordered vasculature with hierarchical structure and had a synergistic effect with vascular endothelial growth factor. Using RNA interference, real-time polymerase chain reaction, and Western blot analysis, we found that IMD alleviated the undesirable effects of vascular endothelial growth factor by restricting the excessive vessel sprouting and uneven lumen formation through the regulation of vascular endothelial-cadherin and identified its receptor on the endothelial cells. Both mitogen-activated protein kinase/extracellular signal–regulated kinase and phosphoinositide 3-kinase/Akt activation were involved in the effects. Furthermore, using experimental tumor models, we demonstrated that IMD was involved in tumor angiogenesis, and the blockade of IMD severely impaired blood supply and eventually inhibited tumor growth.

Conclusion—We demonstrated that IMD played a critical role in the vascular remodeling process and tumor angiogenesis and may serve as a novel target for the development of angiogenesis-based anticancer therapies.

  • Received April 26, 2012.
  • Accepted August 7, 2012.
  • © 2012 American Heart Association, Inc.
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    Intermedin
    Wei Zhang, Li-Jun Wang, Fei Xiao, Yi Wei, Wei Ke and Hong-Bo Xin
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.300185, originally published August 23, 2012
    https://doi.org/10.1161/ATVBAHA.112.300185

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    Intermedin
    Wei Zhang, Li-Jun Wang, Fei Xiao, Yi Wei, Wei Ke and Hong-Bo Xin
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2012;ATVBAHA.112.300185, originally published August 23, 2012
    https://doi.org/10.1161/ATVBAHA.112.300185
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