Abstract 407: Divergent Functions of Thrombospondin Genes in Mammals

• Published in: Circulation research 2017-07, Vol.121 (suppl_1)
• Main Authors: Schips, Tobias G, Vanhoutte, Davy, Brody, Matthew, Correll, Nathan, Tjondrokoesoemo, Andoria, Sargent, Michelle, Maillet, Marjorie, Molkentin, Jeffery D
• Format: Article
• Language: English
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.121.suppl_1.407

Abstract only Thrombospondin (Thbs) proteins are multidomain, matricellular proteins comprised of 5 genes that each share similar domains and have been largely ascribed the same functional characteristics. The Thbs protein family is divided in 2 subgroups based on multimerization as trimers, (group A: Thbs1 and 2), or as pentamers (group B: Thbs3, 4 and 5). Thbs proteins modulate various aspects of cell- matrix interactions. Thbs1 and 2 can also alter angiogenesis and modulate MMP- as well as TGF beta activity. More recently, we have shown that they can also serve an intracellular chaperone function along the secretory pathway in response to ER stress (Lynch et. al. Cell 2012). The overall aim of this study is to functionally compare the two Thbs subgroups and elucidate their involvement in cardiac homeostasis and disease. Hence we analyzed gain and loss of function mouse models for Thbs1 as a representative of group A and Thbs3 for group B. Our overall conclusion was that Thbs4 serves a protective function in the heart while Thbs1 and Thbs3 are either overtly maladaptive or they predispose to worsening heart disease with injury stimulus. Taken together, this is the first study comparing Thbs subfamilies, unraveling previously unrecognized functions of Thbs1 and 3 in the mammalian heart, which appears to oppose the protective function of Thbs4.