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Endothelial-Specific Transgenesis of TNFR2 Promotes Adaptive Arteriogenesis and Angiogenesis
| Content Provider | Scilit |
|---|---|
| Author | Luo, Yan Xu, Zhe Wan, Ting He, Yun Jones, Dennis Zhang, Haifeng Min, Wang |
| Copyright Year | 2010 |
| Description | Journal: Arteriosclerosis, thrombosis, and vascular biology Objective— We have previously shown that the tumor necrosis factor receptor 2 (TNFR2) protein is highly upregulated in vascular endothelium in response to ischemia, and a global deletion of TNFR2 in mice blunts ischemia-induced arteriogenesis and angiogenesis. However, the role of endothelial TNFR2 is not defined. In this study, we used endothelial cell (EC)–specific transgenesis of TNFR2 (TNFR2-TG) in mice to determine the in vivo function of TNFR2 in arteriogenesis and angiogenesis. Methods and Results— In a femoral artery ligation model, TNFR2-TG mice had enhanced limb perfusion recovery and ischemic reserve capacity. TNFR2-TG mice also exhibited significantly enhanced arteriogenesis in the upper limb, whereas capillary formation and maturation in the lower limb were associated with reduction in cellular apoptosis and increased proliferation. Consistently, ischemia-induced TNFR2-dependent bone marrow tyrosine kinase in chromosome X–vascular endothelial growth factor receptor 2 proangiogenic signaling was augmented in TNFR2-TG mice. To further determine whether EC-expressed TNFR2 is sufficient to mediate ischemia-induced angiogenesis, we crossed TNFR2-TG with TNFR2-deficient mice to generate TNFR2-knockout (KO)/TG mice, in which only vascular ECs express TNFR2. The EC-expressed TNFR2 partially rescued the defects of TNFR2-KO in ischemia-induced angiogenic signaling and flow recovery. Conclusion— These in vivo data support a critical role for endothelial TNFR2 in ischemia-mediated adaptive angiogenesis. Therefore, specific expression and activation of TNFR2 in ECs may provide a novel strategy for the treatment of vascular diseases such as coronary artery disease and peripheral arterial disease. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889154/pdf |
| Ending Page | 1314 |
| Page Count | 8 |
| Starting Page | 1307 |
| ISSN | 10795642 |
| e-ISSN | 15244636 |
| DOI | 10.1161/atvbaha.110.204222 |
| Journal | Arteriosclerosis, thrombosis, and vascular biology |
| Issue Number | 7 |
| Volume Number | 30 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2010-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Arteriosclerosis, thrombosis, and vascular biology Peripheral Vascular Disease |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine |
