| First Author | Feil S | Year | 2014 |
| Journal | Circ Res | Volume | 115 |
| Issue | 7 | Pages | 662-7 |
| PubMed ID | 25070003 | Mgi Jnum | J:234898 |
| Mgi Id | MGI:5791057 | Doi | 10.1161/CIRCRESAHA.115.304634 |
| Citation | Feil S, et al. (2014) Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis. Circ Res 115(7):662-7 |
| abstractText | RATIONALE: Atherosclerosis is a widespread and devastating disease, but the origins of cells within atherosclerotic plaques are not well defined. OBJECTIVE: To investigate the specific contribution of vascular smooth muscle cells (SMCs) to atherosclerotic plaque formation by genetic inducible fate mapping in mice. METHODS AND RESULTS: Vascular SMCs were genetically pulse-labeled using the tamoxifen-dependent Cre recombinase, CreER(T2), expressed from the endogenous SM22alpha locus combined with Cre-activatable reporter genes that were integrated into the ROSA26 locus. Mature SMCs in the arterial media were labeled by tamoxifen treatment of young apolipoprotein E-deficient mice before the development of atherosclerosis and then their fate was monitored in older atherosclerotic animals. We found that medial SMCs can undergo clonal expansion and convert to macrophage-like cells that have lost classic SMC marker expression and make up a major component of advanced atherosclerotic lesions. CONCLUSIONS: This study provides strong in vivo evidence for smooth muscle-to-macrophage transdifferentiation and supports an important role of SMC plasticity in atherogenesis. Targeting this type of SMC phenotypic conversion might be a novel strategy for the treatment of atherosclerosis, as well as other diseases with a smooth muscle component. |
