| First Author | Wu W | Year | 2020 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 40 |
| Issue | 8 | Pages | 1870-1890 |
| PubMed ID | 32493169 | Mgi Jnum | J:318642 |
| Mgi Id | MGI:6860193 | Doi | 10.1161/ATVBAHA.120.314465 |
| Citation | Wu W, et al. (2020) Mature Vascular Smooth Muscle Cells, but Not Endothelial Cells, Serve as the Major Cellular Source of Intimal Hyperplasia in Vein Grafts. Arterioscler Thromb Vasc Biol 40(8):1870-1890 |
| abstractText | OBJECTIVE: Neointima formation is a primary cause of intermediate to late vein graft (VG) failure. However, the precise source of neointima cells in VGs remains unclear. Approach and Results: Herein we clarify the relative contributions of mature vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to neointima formation in a mouse model of VG remodeling via the genetic-inducible fate mapping approaches. Regardless of the magnitude of neointima formation, the recipient arterial and the donor venous SMCs contributed approximately 55% of the neointima cells at the anastomotic regions, whereas only donor venous SMCs donated approximately 68% of the neointima cells at the middle bodies. A small portion of the SMC-derived cells became non-SMC cells, most likely vascular stem cells, and constituted 2% to 11% of the cells in each major layer of VGs. In addition, the recipient arterial ECs were the major cellular source of re-endothelialization but did not contribute to neointima formation. The donor venous ECs donated approximately 17% neointima cells in the VGs with mild neointima formation and conditional media from ECs after endothelial-to-mesenchymal transition suppressed vascular SMC dedifferentiation. CONCLUSIONS: The recipient arterial and donor venous mature SMCs dominate but contribute distinctly to intimal hyperplasia at the anastomosis and the middle body regions of VGs. The recipient arterial ECs are the major cellular source of re-endothelialization but do not donate neointima formation in VGs. Only the donor venous ECs undergo endothelial-to-mesenchymal transition. Endothelial-to-mesenchymal transition is marginal for generating neointima cells but is likely required for controlling the quality of VG remodeling. |
