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Angiogenesis-Associated Crosstalk Between Collagens, CXC Chemokines, and Thrombospondin Domain-Containing Proteins

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Abstract

Excessive vascularization is a hallmark of many diseases including cancer, rheumatoid arthritis, diabetic nephropathy, pathologic obesity, age-related macular degeneration, and asthma. Compounds that inhibit angiogenesis represent potential therapeutics for many diseases. Karagiannis and Popel [Proc. Natl. Acad. Sci. USA 105(37):13775–13780, 2008] used a bioinformatics approach to identify more than 100 peptides with sequence homology to known angiogenesis inhibitors. The peptides could be grouped into families by the conserved domain of the proteins they were derived from. The families included type IV collagen fibrils, CXC chemokine ligands, and type I thrombospondin domain-containing proteins. The relationships between these families have received relatively little attention. To investigate these relationships, we approached the problem by placing the families of proteins in the context of the human interactome including >120,000 physical interactions among proteins, genes, and transcripts. We built on a graph theoretic approach to identify proteins that may represent conduits of crosstalk between protein families. We validated these findings by statistical analysis and analysis of a time series gene expression data set taken during angiogenesis. We identified six proteins at the center of the angiogenesis-associated network including three syndecans, MMP9, CD44, and versican. These findings shed light on the complex signaling networks that govern angiogenesis phenomena.

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Acknowledgments

The work was supported by NIH grants R01 HL101200 and R01 CA138264. The authors would like to thank Emmanouil Karagiannis for helpful discussions at the initial stage of the project. We would also like to thank Sofie Mellberg and Lena Claesson-Welsh for use of their time series gene expression dataset. CGR implemented the method, performed the analysis, generated the images and wrote the paper. ASP and JSB designed the study and edited the paper.

Conflict of Interests

The authors declare no competing interests.

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Authors and Affiliations

  1. Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, 720 Rutland Avenue, 613 Traylor Bldg, Baltimore, MD, 21205, USA

    Corban G. Rivera, Joel S. Bader & Aleksander S. Popel

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  1. Corban G. Rivera
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  2. Joel S. Bader
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  3. Aleksander S. Popel
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Correspondence to Corban G. Rivera.

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Associate Editor Sriram Neelamegham oversaw the review of this article.

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Rivera, C.G., Bader, J.S. & Popel, A.S. Angiogenesis-Associated Crosstalk Between Collagens, CXC Chemokines, and Thrombospondin Domain-Containing Proteins. Ann Biomed Eng 39, 2213–2222 (2011). https://doi.org/10.1007/s10439-011-0325-2

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  • DOI: https://doi.org/10.1007/s10439-011-0325-2

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