Preservation of rabbit aorta elastin from degradation by gingival fibroblasts in an ex vivo model.
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.


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.
Gogly
Bruno
B
Inserm U 849-Université Paris-Descartes, Faculté de Médecine de Necker, 156, rue de Vaugirard, Paris 75730 Cedex 15 France.
Naveau
Adrien
A
Fournier
Benjamin
B
Reinald
Nicoleta
N
Durand
Eric
E
Brasselet
Camille
C
Coulomb
Bernard
B
Lafont
Antoine
A
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000628:therapy; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004549:Elastin / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011817:Rabbits; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
D019715:Tissue Inhibitor of Metalloproteinase-1; D004549:Elastin; D020780:Matrix Metalloproteinase 9