Journal
MICROVASCULAR RESEARCH
Volume 74, Issue 2-3, Pages 90-99Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2007.04.007
Keywords
thrombospondin; angiogenesis; antiangiogenic therapy; endothelial cell
Categories
Funding
- NCI NIH HHS [P01 CA092644-01A10004, P01 CA092644] Funding Source: Medline
- NHLBI NIH HHS [R01 HL049081-14, R01 HL049081] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P01CA092644] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL049081] Funding Source: NIH RePORTER
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Thrombospondins (TSPs) are a family of extracellular matrix proteins that regulate tissue genesis and remodeling. TSP-1 plays a pivotal role in the regulation of both physiological and pathological angiogenesis. The inhibitory effects of TSP-1 on angiogenesis have been established in numerous experimental models. Among other TSP members, TSP-2 has equivalent domain structure as TSP-1 and shares most ftinctions of TSP-1. The mechanisms by which TSP-1 and -2 inhibit angiogenesis can be broadly characterized as direct effects on vascular endothelial cells and indirect effects on the various angiogenic regulators. The fact that TSP-1 and -2 are potent endogetious angiogenic inhibitors has prompted studies to explore their therapeutic applications, and detailed understanding of the mechanisms of action of TSP-1 and -2 has facilitated the design of therapeutic strategies to optimize these activities. The therapeutic effects can be achieved by up-regulation of endogenous TSPs, or by the delivery of recombinant proteins or synthetic peptides that contain sequences from the angiogenic domain of TSP-1. In this article, we review the progress in thrombospondin-based antiangiogenic therapy and discuss the perspectives on the significant challenges that remain. (C) 2007 Elsevier Inc. All rights reserved.
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