| First Author | Rossdeutsch A | Year | 2012 |
| Journal | Circ Res | Volume | 111 |
| Issue | 4 | Pages | e89-102 |
| PubMed ID | 22723298 | Mgi Jnum | J:195902 |
| Mgi Id | MGI:5486118 | Doi | 10.1161/CIRCRESAHA.111.259846 |
| Citation | Rossdeutsch A, et al. (2012) Essential role for thymosin beta4 in regulating vascular smooth muscle cell development and vessel wall stability. Circ Res 111(4):e89-102 |
| abstractText | RATIONALE: Compromised development of blood vessel walls leads to vascular instability that may predispose to aneurysm with risk of rupture and lethal hemorrhage. There is currently a lack of insight into developmental insults that may define the molecular and cellular characteristics of initiating and perpetrating factors in adult aneurismal disease. OBJECTIVE: To investigate a role for the actin-binding protein thymosin beta4 (Tbeta4), previously shown to be proangiogenic, in mural cell development and vascular wall stability. METHODS AND RESULTS: Phenotypic analyses of both global and endothelial-specific loss-of-function Tbeta4 mouse models revealed a proportion of Tbeta4-null embryos with vascular hemorrhage coincident with a reduction in smooth muscle cell coverage of their developing vessels. Mechanistic studies revealed that extracellular Tbeta4 can stimulate differentiation of mesodermal progenitor cells to a mature mural cell phenotype through activation of the transforming growth factor-beta (TGFbeta) pathway and that reduced TGFbeta signaling correlates with the severity of hemorrhagic phenotype in Tbeta4-null vasculature. CONCLUSIONS: Tbeta4 is a novel endothelial secreted trophic factor that functions synergistically with TGFbeta to regulate mural cell development and vascular wall stability. These findings have important implications for understanding congenital anomalies that may be causative for adult-onset vascular instability. |
