title: Comparative study of abdominal and thoracic aortic aneurysms: their pathogenesis and a gingival fibroblasts-based ex vivo treatment.
abstract: Aortic aneurysms (AAs) consist of slow proteolysis and loss of both collagen and elastin matrix in the aorta wall, leading to wall dilation, weakening and rupture in well-advanced lesions. This can occur in both abdominal aorta (Abdominal Aortic Aneurysm: AAA) and thoracic aorta (Thoracic Aortic Aneurysm: TAA). To date, no non-surgical therapy has been proposed to slow or stop AA progression. Previously published preclinical studies from our team using an aneurysm rabbit model showed a promising concept for treatment of AAs with gingival fibroblast (GFs) which are readily available cells. In this study, we investigated the possible tissue repair of human AAAs and TAAs using ex vivo models co-cultured with GFs. Histological analysis showed that TAA and AAA are two distinct pathologies. Both lesions presented destruction of the aorta wall, highly evidenced in AAA samples. The results have confirmed the presence of the bacterial Porphyromonas gingivalis (Pg) protein in all AAA samples, but not in TAA samples, indicating the possible role of an infectious factor in the developing and progression of AAA lesions compared to TAA. The co-culture of GFs with AA lesions shows increased expression of TIMP-1, the inhibitor of the aneurysm severity marker MMP-9. Our study indicates that GFs might ameliorate aorta wall reestablishment in both AA types by their regenerative and immunomodulatory capacities. It also demonstrates the possible infectious cause of AAA compared with TAA that may explain their different behavior.
authors.affiliation: Centre de recherche des cordeliers, INSERM UMRS 1138, Team 5, Laboratory of Molecular Oral Pathophysiology, Paris, France ; Paris-Est University, Créteil, France ; Paris-Descartes University, Paris, France ; A. Chenevier/H.Mondor Hospitals, Dental Department, APHP, Créteil, France.
authors.forename: Hafida
authors.initials: H
authors.lastname: Cherifi
authors.affiliation: Centre de recherche des cordeliers, INSERM UMRS 1138, Team 5, Laboratory of Molecular Oral Pathophysiology, Paris, France ; Paris-Est University, Créteil, France ; Paris-Descartes University, Paris, France ; A. Chenevier/H.Mondor Hospitals, Dental Department, APHP, Créteil, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gogly
authors.affiliation: Centre de recherche des cordeliers, INSERM UMRS 1138, Team 5, Laboratory of Molecular Oral Pathophysiology, Paris, France ; Paris-Est University, Créteil, France ; Paris-Descartes University, Paris, France ; A. Chenevier/H.Mondor Hospitals, Dental Department, APHP, Créteil, France.
authors.forename: Ludwig-Stanislas
authors.initials: LS
authors.lastname: Loison-Robert
authors.affiliation: Paris centre de recherche cardiovasculaire, INSERM UMRS 970, Team 11, Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Couty
authors.affiliation: Centre de recherche des cordeliers, INSERM UMRS 1138, Team 5, Laboratory of Molecular Oral Pathophysiology, Paris, France ; Paris-Descartes University, Paris, France.
authors.forename: François Côme
authors.initials: FC
authors.lastname: Ferré
authors.affiliation: Centre de recherche des cordeliers, INSERM UMRS 1138, Team 5, Laboratory of Molecular Oral Pathophysiology, Paris, France ; Paris-Est University, Créteil, France ; A. Chenevier/H.Mondor Hospitals, Dental Department, APHP, Créteil, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Nassif
authors.affiliation: Paris centre de recherche cardiovasculaire, INSERM UMRS 970, Team 11, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lafont
authors.affiliation: Centre de recherche des cordeliers, INSERM UMRS 1138, Team 5, Laboratory of Molecular Oral Pathophysiology, Paris, France ; Paris-Diderot University, Paris, France ; Rothschild Hospital, Dental Department, AP-HP, Paris, France.
authors.forename: Benjamin Pj
authors.initials: BP
authors.lastname: Fournier
keywords: Aortic aneurysm; Cell therapy; Gingival fibroblast; Porphyromonas gingivalis