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on July 19, 2007

Arteriosclerosis, Thrombosis, and Vascular Biology. 2007
Published online before print July 19, 2007, doi: 10.1161/ATVBAHA.107.140640
A more recent version of this article appeared on September 1, 2007
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Submitted on January 28, 2007
Accepted on June 19, 2007

Preservation of Rabbit Aorta Elastin From Degradation by Gingival Fibroblasts in an Ex Vivo Model

Bruno Gogly ; Adrien Naveau ; Benjamin Fournier ; Nicoleta Reinald ; Eric Durand ; Camille Brasselet ; Bernard Coulomb ; and Antoine Lafont *

From the Paris-Descartes University, Paris-Descartes Medicine Faculty, INSERM U849 (B.G., A.N., B.F., N.R., B.C., A.L.), the Dental Department, Hopital Albert Chenevier (B.G., A.N., B.F., N.R., E.D., C.B.), and the Cardiology Department, Hopital Europeen Georges Pompidou (E.D., C.B., A.L.), Paris, France.

* To whom correspondence should be addressed. E-mail: lafont{at}necker.fr.

Objective--Embryo-like gingival healing properties are attributed to the gingival fibroblast (GF) and could be used as a model for other types of healing dysfunctions. Abdominal aortic aneurysm (AAA) formation is associated with elastin degradation and increase in matrix metalloproteinase (MMP)-9 activity. We aimed to validate the concept of using GF healing properties in arteries.

Methods and Results--We evaluated MMP-9 and its tissue inhibitor (TIMP-1) in rabbit aortic rings cultured in collagen gels with or without GFs and observed throughout 21 days. We also performed cocultures of human smooth muscle cells (hSMCs) with either gingival, dermal, or adventitial fibroblasts, and alone (control). In control arteries, elastic fibers became spontaneously sparse. In presence of GFs, elastic fibers were preserved. There was a dramatically reduced protein level of MMP-9 in coculture of aorta and GFs, in contrast with control aorta. MMP-9 expression was unaffected by GFs. MMP-9 inhibition was related to increased TIMP-1 secretion, TIMP-1 forming a complex with MMP-9. Cell cocultures of hSMC with GFs showed similar results. Dermal and adventitial fibroblasts did not affect MMP-9.

Conclusions--Elastic fiber degradation was specifically preserved by GFs via reduction of MMP-9 protein level by increasing TIMP-1 synthesis. Vascular transfer of gingival fibroblasts could be a promising approach to treat AAA.


Key words: gingival fibroblast • elastin • MMP-9 • TIMP-1 • aneurysm