Gingival fibroblasts protect against experimental abdominal aortic aneurysm development and rupture through tissue inhibitor of metalloproteinase-1 production.
Andreas Giraud,Lynda Zeboudj,Marie Vandestienne,Jérémie Joffre,Bruno Esposito,Stephane Potteaux,José Vilar,Daniela Cabuzu,Johannes Kluwe,Sylvie Seguier,Alain Tedgui,Ziad Mallat,Ziad Mallat,Antoine Lafont,Hafid Ait-Oufella,Hafid Ait-Oufella +15 more
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GF cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1.Abstract:
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.read more
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Journal ArticleDOI
Pharmacologic Management of Aneurysms.
TL;DR: No medical therapy can be recommended for the stabilization of aortic aneurysms, and preclinical models more reflective of human pathophysiology, identification of biomarkers to predict severity of disease progression, and improved design of clinical trials may more rapidly advance the opportunities in this important field.
Journal ArticleDOI
Knockdown of lncRNA PVT1 Inhibits Vascular Smooth Muscle Cell Apoptosis and Extracellular Matrix Disruption in a Murine Abdominal Aortic Aneurysm Model.
TL;DR: It is demonstrated that knockdown of lncRNA PVT1 suppresses VSMC apoptosis, ECM disruption, and serum pro-inflammatory cytokines in a murine Ang II-induced AAA model.
Journal ArticleDOI
Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling.
Icía Santos-Zas,Jeremie Lemarié,Ivana Zlatanova,Marine Cachanado,Jean-Christophe Seghezzi,Benamer H,Pascal Goube,Marie Vandestienne,Raphael Cohen,Maya Ezzo,Vincent Duval,Yujiao Zhang,Jin-Bo Su,Alain Bizé,Lucien Sambin,Philippe Bonnin,Maxime Branchereau,Christophe Heymes,Corinne Tanchot,José Vilar,Clément Delacroix,Jean-Sébastien Hulot,Clément Cochain,Patrick Bruneval,Nicolas Danchin,Alain Tedgui,Ziad Mallat,Ziad Mallat,Tabassome Simon,Bijan Ghaleh,Jean-Sébastien Silvestre,Hafid Ait-Oufella +31 more
TL;DR: In this paper, the authors show that following acute myocardial infarction in mice, CD8+ T lymphocytes are recruited and activated in the ischemic heart tissue and release Granzyme B, leading to cardiomyocyte apoptosis, adverse ventricular remodeling and deterioration of myocardia.
Journal ArticleDOI
T Cells Are Dominant Population in Human Abdominal Aortic Aneurysms and Their Infiltration in the Perivascular Tissue Correlates With Disease Severity.
Agnieszka Sagan,Tomasz Mikolajczyk,Wojciech Mrowiecki,Neil MacRitchie,Kevin P. Daly,Alan Meldrum,Serena Migliarino,Christian Delles,Karol Urbanski,Grzegorz Filip,Bogusław Kapelak,Pasquale Maffia,Pasquale Maffia,Rhian M. Touyz,Tomasz J. Guzik,Tomasz J. Guzik +15 more
TL;DR: An important role is highlighted for PVT as a reservoir of T lymphocytes and potentially as a key site in modulating the underlying inflammation in AAA.
Journal ArticleDOI
IL (Interleukin)-33 Suppresses Abdominal Aortic Aneurysm by Enhancing Regulatory T-Cell Expansion and Activity.
Jingyong Li,Ni Xia,Shuang Wen,Dan Li,Yuzhi Lu,Muyang Gu,Tingting Tang,Jiao Jiao,Bingjie Lv,Shaofang Nie,Mengyang Liao,Yuhua Liao,Xiang-Ping Yang,Yu Hu,Guo-Ping Shi,Xiang Cheng +15 more
TL;DR: A role of IL-33 is established in protecting mice from AAA formation by enhancing ST2-dependent aortic and systemic regulatory T-cell expansion and their immunosuppressive activities.
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