| First Author | Chen PY | Year | 2020 |
| Journal | Cell Stem Cell | Volume | 26 |
| Issue | 4 | Pages | 542-557.e11 |
| PubMed ID | 32243809 | Mgi Jnum | J:307038 |
| Mgi Id | MGI:6710366 | Doi | 10.1016/j.stem.2020.02.013 |
| Citation | Chen PY, et al. (2020) Smooth Muscle Cell Reprogramming in Aortic Aneurysms. Cell Stem Cell 26(4):542-557.e11 |
| abstractText | The etiology of aortic aneurysms is poorly understood, but it is associated with atherosclerosis, hypercholesterolemia, and abnormal transforming growth factor beta (TGF-beta) signaling in smooth muscle. Here, we investigated the interactions between these different factors in aortic aneurysm development and identified a key role for smooth muscle cell (SMC) reprogramming into a mesenchymal stem cell (MSC)-like state. SMC-specific ablation of TGF-beta signaling in Apoe(-/-) mice on a hypercholesterolemic diet led to development of aortic aneurysms exhibiting all the features of human disease, which was associated with transdifferentiation of a subset of contractile SMCs into an MSC-like intermediate state that generated osteoblasts, chondrocytes, adipocytes, and macrophages. This combination of medial SMC loss with marked increases in non-SMC aortic cell mass induced exuberant growth and dilation of the aorta, calcification and ossification of the aortic wall, and inflammation, resulting in aneurysm development. |
