Angiotensin peptides have been demonstrated to modulate cellular proliferation, angiogenesis, and dermal repair. In this report, the effects of an analogue of the active
angiotensin peptide angiotensin(1-7), namely norLeu3-angiotensin(1-7) (NorLeu3-A(1-7)), on the healing of epithelial
wounds are presented. Three models were used to evaluate the normal (rats) and delayed (diabetic mice) healing responses of full-thickness excision
wounds and the healing responses of full-thickness incision
wounds (rats).
NorLeu3-A(1-7) was superior to the naturally occurring
angiotensin peptide angiotensin(1-7) and to
Regranex (Ortho McNeil, Somerville, N.J.) (a formulation of recombinant
platelet-derived growth factor used clinically for the treatment of diabetic
ulcers) in accelerating tissue repair. By day 9 (normal rats) and day 11 (diabetic mice), the differences in the rates of closure of full-thickness excision
wounds between
NorLeu3-A(1-7) and
Regranex were statistically significant (n = 5 per group). Full healing was observed for 60 percent of the diabetic mice treated topically with
NorLeu3-A(1-7) by day 18 after injury, at which time full healing of
wounds on placebo-treated or
Regranex-treated diabetic mice was not observed. In the rat incision model, accelerated healing and reduced gross appearance of scarification were observed. Administration of
NorLeu3-A(1-7) reduced
fibrosis and
scarring in the healing
wounds. This action was more pronounced with longer administration of the
peptide after injury. In fact, if systemic administration of the
peptide (NorLeu3-A(1-7)) was continued during the remodeling phase, then the formation of new adnexal structures at the center of full-thickness excision
wounds was observed, with an increase in the appearance of small immature hair follicles at the sites of the excision
wounds. The action of this
peptide was blocked by the AT receptor antagonist d-Ala7-angiotensin(1-7), which suggests that this receptor is involved in the healing responses to exogenous
NorLeu3-A(1-7). These data suggest that this novel
angiotensin peptide has the potential to be of benefit in accelerating
wound repair and reducing
scar formation.