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

Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Annals of Biomedical Engineering (Impact Factor: 3.23). 05/2011; 39(8):2213-22. DOI: 10.1007/s10439-011-0325-2
Source: PubMed


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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Available from: Aleksander S Popel,
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    • "Angiogenesis, the growth of new blood vessels from existing vasculature , is critical whenever tissues undergo extensive remodeling processes , including during normal growth and development, wound healing (Bao et al., 2009; Folkman and Shing, 1992), the female reproductive cycle (Demir et al., 2010), mammary gland development during pregnancy and lactation (Andres and Djonov, 2010), and the expansion of fat mass in obesity (Cao, 2007; Lijnen, 2008). Excessive vascularization is a hallmark of many diseases including cancer, rheumatoid arthritis , diabetic nephropathy, pathologic obesity, age-related macular degeneration and asthma (Rivera et al., 2011). Angiogenesis is thus required to sustain malignant cells with nutrients and oxygen to assist their growth. "
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