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  • Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production.

Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production.

Cardiovascular research (2017-06-06)
Andreas Giraud, Lynda Zeboudj, Marie Vandestienne, Jérémie Joffre, Bruno Esposito, Stéphane Potteaux, José Vilar, Daniela Cabuzu, Johannes Kluwe, Sylvie Seguier, Alain Tedgui, Ziad Mallat, Antoine Lafont, Hafid Ait-Oufella
摘要

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. 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-β, 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-β 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. GF cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1.

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Sigma-Aldrich
弹性蛋白酶 来源于猪胰腺, Type I, ≥4.0 units/mg protein