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Vascular Biology |
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.
Correspondence to Antoine LAFONT, Inserm U 849 - Université Paris-Descartes, Faculté de Médecine de Necker, 156, rue de Vaugirard, Paris 75730 Cedex 15 France. 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.
We aimed to validate the concept of using gingival fibroblast healing properties in arteries. Elastic fiber degradation was specifically preserved by gingival fibroblasts via reduction of MMP-9 activity by increasing TIMP-1 synthesis. Vascular transfer of gingival fibroblasts could be a promising approach to treat abdominal aortic aneurisms.
Key Words: gingival fibroblast elastin MMP-9 TIMP-1 aneurysm
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