| First Author | Moriya J | Year | 2010 |
| Journal | Circ Res | Volume | 106 |
| Issue | 2 | Pages | 391-8 |
| PubMed ID | 19940264 | Mgi Jnum | J:170057 |
| Mgi Id | MGI:4943844 | Doi | 10.1161/CIRCRESAHA.109.210815 |
| Citation | Moriya J, et al. (2010) Inhibition of semaphorin as a novel strategy for therapeutic angiogenesis. Circ Res 106(2):391-8 |
| abstractText | RATIONALE: The axon-guiding molecules known as semaphorins and their receptors (plexins) regulate the vascular pattern and play an important role in the development of vascular network during embryogenesis. Semaphorin (Sema)3E is one of the class 3 semaphorins, and plexinD1 is known to be its receptor. Although these molecules have a role in embryonic vascular development, it remains unclear whether the Sema3E/plexinD1 axis is involved in postnatal angiogenesis. OBJECTIVE: The objective of this study was to elucidate the role of Sema3E/plexinD1 in postnatal angiogenesis. METHODS AND RESULTS: Sema3E inhibited cell growth and tube formation by suppressing the vascular endothelial growth factor (VEGF) signaling pathway. Expression of Sema3E and plexinD1 was markedly upregulated in ischemic limbs of mice (2.5- and 4.5-fold increase for Sema3E and plexinD1, respectively), and inhibition of this pathway by introduction of the plexinD1-Fc gene or disruption of Sema3E led to a significant increase of blood flow recovery (1.6- and 1.5-fold increase for the plexinD1-Fc gene treatment and Sema3E disruption, respectively). Hypoxia activated the tumor suppressor protein p53, thereby upregulating Sema3E expression. Expression of p53 and Sema3E was enhanced in diabetic mice compared with normal mice (2- and 1.3-fold increase for p53 and Sema3E, respectively). Consequently, neovascularization after VEGF treatment was poor in the ischemic tissues of diabetic mice, whereas treatment with VEGF plus plexinD1-Fc markedly improved neovascularization. CONCLUSIONS: These results indicate that inhibition of Sema3E may be a novel strategy for therapeutic angiogenesis, especially when VEGF is ineffective. |
