| First Author | Nemenoff RA | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 6 | Pages | 1300-8 |
| PubMed ID | 21415388 | Mgi Jnum | J:191476 |
| Mgi Id | MGI:5461800 | Doi | 10.1161/ATVBAHA.111.223701 |
| Citation | Nemenoff RA, et al. (2011) SDF-1alpha induction in mature smooth muscle cells by inactivation of PTEN is a critical mediator of exacerbated injury-induced neointima formation. Arterioscler Thromb Vasc Biol 31(6):1300-8 |
| abstractText | OBJECTIVE: PTEN inactivation selectively in smooth muscle cells (SMC) initiates multiple downstream events driving neointima formation, including SMC cytokine/chemokine production, in particular stromal cell-derived factor-1alpha (SDF-1alpha). We investigated the effects of SDF-1alpha on resident SMC and bone marrow-derived cells and in mediating neointima formation. METHODS AND RESULTS: Inducible, SMC-specific PTEN knockout mice (PTEN iKO) were bred to floxed-stop ROSA26-beta-galactosidase (betaGal) mice to fate-map mature SMC in response to injury; mice received wild-type green fluorescent protein-labeled bone marrow to track recruitment. Following wire-induced femoral artery injury, betaGal(+) SMC accumulated in the intima and adventitia. Compared with wild-type, PTEN iKO mice exhibited massive neointima formation, increased replicating intimal and medial betaGal(+)SMC, and enhanced vascular recruitment of bone marrow cells following injury. Inhibiting SDF-1alpha blocked these events and reversed enhanced neointima formation observed in PTEN iKO mice. Most recruited green fluorescent protein(+) cells stained positive for macrophage markers but not SMC markers. SMC-macrophage interactions resulted in a persistent SMC inflammatory phenotype that was dependent on SMC PTEN and SDF-1alpha expression. CONCLUSION: Resident SMC play a multifaceted role in neointima formation by contributing the majority of neointimal cells, regulating recruitment of inflammatory cells, and contributing to adventitial remodeling. The SMC PTEN-SDF-1alpha axis is a critical regulator of these events. |
