| First Author | Muppala S | Year | 2015 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 35 |
| Issue | 9 | Pages | 1975-86 |
| PubMed ID | 26139464 | Mgi Jnum | J:301119 |
| Mgi Id | MGI:6505382 | Doi | 10.1161/ATVBAHA.115.305912 |
| Citation | Muppala S, et al. (2015) Proangiogenic Properties of Thrombospondin-4. Arterioscler Thromb Vasc Biol 35(9):1975-86 |
| abstractText | OBJECTIVE: 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. APPROACH AND RESULTS: The effect of TSP-4 in in vivo angiogenesis models and its effect on angiogenesis-related properties in cultured cells were assessed using Thbs4(-/-) mice, endothelial cells (EC) derived from these mice, and recombinant TSP-4. Angiogenesis was decreased in Thbs4(-/-) 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 Thbs4(-/-) 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 alpha2 and gabapentin receptor alpha2delta-1 were identified as receptors involved in regulation of EC adhesion, migration, and proliferation by TSP-4. CONCLUSION: TSP-4, an extracellular matrix protein previously associated with tissue remodeling, is now demonstrated to possess proangiogenic activity. |
