Proangiogenic Properties of Thrombospondin-4. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Muppala, Santoshi; Frolova, Ella; Xiao, Roy; Krukovets, Irene; Yoon, Suzy; Hoppe, George; Vasanji, Amit; Plow, Edward; Stenina-Adognravi, Olga
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 35:Issue 9(2015)
• Publication Date: 2015-09
• Subjects: Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.115.305912
• Languages: English
• ISSNs: 1079-5642

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective—</title> <p>Thrombospondin-4 (TSP-4) is 1 of the 5 members of the thrombospondin protein family. TSP-1 and TSP-2 are potent antiangiogenic proteins. However, angiogenic properties of the 3 other TSPs, which do not contain the domains associated with the antiangiogeneic activity of TSP-1 and TSP-2, have not been explored. In our previous studies, we found that TSP-4 is expressed in the vascular matrix of blood vessels of various sizes and is especially abundant in capillaries. We sought to identify the function of TSP-4 in the regulation of angiogenesis.</p> </sec> <sec> <title>Approach and Results—</title> <p>The effect of TSP-4 in in vivo angiogenesis models and its effect on angiogenesis-related properties in cultured cells were assessed using <italic>Thbs4</italic><sup>−/−</sup> mice, endothelial cells (EC) derived from these mice, and recombinant TSP-4. Angiogenesis was decreased in <italic>Thbs4</italic><sup>−/−</sup> mice compared with wild-type mice. TSP-4 was detected in the lumen of the growing blood vessels. Mice expressing the P387 TSP-4 variant, which was previously associated with coronary artery disease and found to be more active in its cellular interactions, displayed greater angiogenesis compared with A387 form. Lung EC from <italic>Thbs4</italic><sup>−/−</sup> mice exhibited decreased adhesion, migration, and proliferation capacities compared with EC from wild-type mice. Recombinant TSP-4 promoted proliferation and the migration of EC. Integrin α<sub>2</sub> and gabapentin receptor α<sub>2</sub>δ-1 were identified as receptors involved in regulation of EC adhesion, migration, and proliferation by TSP-4.</p> </sec> <sec> <title>Conclusion—</title> <p>TSP-4, an extracellular matrix protein previously associated with tissue remodeling, is now demonstrated to possess proangiogenic activity.</p> </sec> </abstract>