CD36-TSP-HRGP interactions in the regulation of angiogenesis. Curr Pharm Des 2007;13(35):3559-67
Date
01/29/2008Pubmed ID
18220792DOI
10.2174/138161207782794185Scopus ID
2-s2.0-36949022250 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
Thrombospondin (TSP)-1 and -2 are potent inhibitors of angiogenesis in vivo and of microvascular endothelial cell responses to angiogenic factors in vitro. The anti-angiogenic activity of thrombospondins is contained in a structural domain known as the TSP type I repeat or TSR. TSR domains are present in many other proteins, several of which have also been shown to have anti-angiogenic activity and a peptide-mimetic drug based on the domain is in clinical trials as an anti-angiogenic anti-cancer therapy. We have identified CD36 as the endothelial cell receptor for TSP-1 and -2 and showed that it is necessary for their anti-angiogenic activity. CD36-mediated anti-angiogenic activity in endothelial cells is due to its ability to activate a specific signaling cascade that results in diversion of a pro-angiogenic response to an apoptotic response. Recently we identified a circulating protein, histidine-rich glycoprotein (HRGP), that contains a CD36 homology domain and that acts as a soluble decoy to block the anti-angiogenic activities of TSPs, thereby promoting angiogenesis. The tripartite interactions among CD36, TSR domains and HRGP in tissues may play an important role in regulating physiological and pathological angiogenesis.
Author List
Silverstein RL, Febbraio MAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis Inducing AgentsAngiogenesis Inhibitors
Animals
Antineoplastic Agents
Apoptosis
CD36 Antigens
Endothelial Cells
Humans
Models, Molecular
Neovascularization, Pathologic
Neovascularization, Physiologic
Protein Conformation
Protein Structure, Tertiary
Proteins
Signal Transduction
Thrombospondin 1
Thrombospondins
