{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:14:03Z","timestamp":1791195243671,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats: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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              The effect of TSP-4 in in vivo angiogenesis models and its effect on angiogenesis-related properties in cultured cells were assessed using\n              <jats:italic>Thbs4<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, endothelial cells (EC) derived from these mice, and recombinant TSP-4. Angiogenesis was decreased in\n              <jats:italic>Thbs4<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              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\n              <jats:italic>Thbs4<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              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 \u03b1\n              <jats:sub>2<\/jats:sub>\n              and gabapentin receptor \u03b1\n              <jats:sub>2<\/jats:sub>\n              \u03b4-1 were identified as receptors involved in regulation of EC adhesion, migration, and proliferation by TSP-4.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>TSP-4, an extracellular matrix protein previously associated with tissue remodeling, is now demonstrated to possess proangiogenic activity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.305912","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T14:46:25Z","timestamp":1435934785000},"page":"1975-1986","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["Proangiogenic Properties of Thrombospondin-4"],"prefix":"10.1161","volume":"35","author":[{"given":"Santoshi","family":"Muppala","sequence":"first","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Frolova","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Xiao","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Krukovets","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy","family":"Yoon","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Hoppe","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Vasanji","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Plow","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH (A.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Stenina-Adognravi","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Cardiology (S.M., E.F., R.X., I.K., E.P., O.S.-A.), and Cole Eye Institute (S.Y., G.H.), Cleveland Clinic, OH; and ImageIQ Inc, Cleveland, OH 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