| First Author | Giraud A | Year | 2017 |
| Journal | Cardiovasc Res | Volume | 113 |
| Issue | 11 | Pages | 1364-1375 |
| PubMed ID | 28582477 | Mgi Jnum | J:258576 |
| Mgi Id | MGI:6142422 | Doi | 10.1093/cvr/cvx110 |
| Citation | Giraud A, et al. (2017) Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production. Cardiovasc Res 113(11):1364-1375 |
| abstractText | Aims: Abdominal aortic aneurysm (AAA), frequently diagnosed in old patients, is characterized by chronic inflammation, vascular cell apoptosis and metalloproteinase-mediated extracellular matrix destruction. Despite improvement in the understanding of the pathophysiology of aortic aneurysm, no pharmacological treatment is yet available to limit dilatation and/or rupture. We previously reported that human gingival fibroblasts (GFs) can reduce carotid artery dilatation in a rabbit model of elastase-induced aneurysm. Here, we sought to investigate the mechanisms of GF-mediated vascular protection in two different models of aortic aneurysm growth and rupture in mice. Methods and results: In vitro, mouse GFs proliferated and produced large amounts of anti-inflammatory cytokines and tissue inhibitor of metalloproteinase-1 (Timp-1). GFs deposited on the adventitia of abdominal aorta survived, proliferated, and organized as a layer structure. Furthermore, GFs locally produced Il-10, TGF-beta, and Timp-1. In a mouse elastase-induced AAA model, GFs prevented both macrophage and lymphocyte accumulations, matrix degradation, and aneurysm growth. In an Angiotensin II/anti-TGF-beta model of aneurysm rupture, GF cell-based treatment limited the extent of aortic dissection, prevented abdominal aortic rupture, and increased survival. Specific deletion of Timp-1 in GFs abolished the beneficial effect of cell therapy in both AAA mouse models. Conclusions: GF cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1. |
