Abstract
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 antiangiogenic activity in endothelial cells is due to its ability to activate a specific signaling cascade that results in diversion of a proangiogenic 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.
Keywords: Angiogenesis, CD36, TSP-1, TSP-2, HRGP, endothelial cells
Current Pharmaceutical Design
Title: CD36-TSP-HRGP Interactions in the Regulation of Angiogenesis
Volume: 13 Issue: 35
Author(s): Roy L. Silverstein and Maria Febbraio
Affiliation:
Keywords: Angiogenesis, CD36, TSP-1, TSP-2, HRGP, endothelial cells
Abstract: 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 antiangiogenic activity in endothelial cells is due to its ability to activate a specific signaling cascade that results in diversion of a proangiogenic 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.
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Cite this article as:
Silverstein L. Roy and Febbraio Maria, CD36-TSP-HRGP Interactions in the Regulation of Angiogenesis, Current Pharmaceutical Design 2007; 13 (35) . https://dx.doi.org/10.2174/138161207782794185
DOI https://dx.doi.org/10.2174/138161207782794185 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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