Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production
Standard
Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production. / Giraud, Andreas; Zeboudj, Lynda; Vandestienne, Marie; Joffre, Jérémie; Esposito, Bruno; Potteaux, Stéphane; Vilar, José; Cabuzu, Daniela; Kluwe, Johannes; Seguier, Sylvie; Tedgui, Alain; Mallat, Ziad; Lafont, Antoine; Ait-Oufella, Hafid.
In: CARDIOVASC RES, Vol. 113, No. 11, 01.09.2017, p. 1364-1375.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production
AU - Giraud, Andreas
AU - Zeboudj, Lynda
AU - Vandestienne, Marie
AU - Joffre, Jérémie
AU - Esposito, Bruno
AU - Potteaux, Stéphane
AU - Vilar, José
AU - Cabuzu, Daniela
AU - Kluwe, Johannes
AU - Seguier, Sylvie
AU - Tedgui, Alain
AU - Mallat, Ziad
AU - Lafont, Antoine
AU - Ait-Oufella, Hafid
N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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-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.Conclusions: GF cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1.
AB - 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-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.Conclusions: GF cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1.
KW - Angiotensin II
KW - Animals
KW - Aorta, Abdominal
KW - Aortic Aneurysm, Abdominal
KW - Aortic Rupture
KW - Disease Models, Animal
KW - Extracellular Matrix
KW - Fibroblasts
KW - Gingiva
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Protective Agents
KW - Tissue Inhibitor of Metalloproteinase-1
KW - Transforming Growth Factor beta
KW - Journal Article
U2 - 10.1093/cvr/cvx110
DO - 10.1093/cvr/cvx110
M3 - SCORING: Journal article
C2 - 28582477
VL - 113
SP - 1364
EP - 1375
JO - CARDIOVASC RES
JF - CARDIOVASC RES
SN - 0008-6363
IS - 11
ER -