Development of angiotensin (1-7) as an agent to accelerate dermal repair.
Angiotensin II has been shown to be a potent agent in the acceleration of wound repair. Angiotensin (1-7), a fragment of angiotensin II that is not hypertensive, was found to be comparable to angiotensin II in accelerating dermal healing. This activity was evaluated in four models: rat and diabetic mouse full-thickness excisional wounds; rat random flap; and guinea pig partial thickness thermal injury. In all models, angiotensin (1-7) was comparable to angiotensin II. Angiotensin (1-7) accelerated the closure of wounds in diabetic mice and rats. In diabetic mice the resultant tissue at day 25 after injury was more comparable to normal tissue than the fibrotic scar observed in placebo-treated wounds. In the random flap model, angiotensin (1-7) was comparable to angiotensin II in maintaining flap viability (approximately 82%) and flap survival (40%). Finally, angiotensin (1-7) increased proliferation in the hair follicles at the edge of the wound and site of thermal injury, and the number of patent blood vessels on day 7 after partial thickness thermal injury. These data may be partially explained by the effect of angiotensin II and angiotensin (1-7) on keratinocyte proliferation. While platelet-derived growth factor had no effect on keratinocyte proliferation, angiotensin II and angiotensin (1-7) significantly increased keratinocyte proliferation. These data show that angiotensin(1-7) is comparable to angiotensin II in accelerating skin repair. Furthermore, the hypertensive and wound healing effects can be separated within the family of angiotensin peptides.
Rodgers
K
K
University of Southern California, Keck School of Medicine, Los Angeles, California, USA. krogers@hsc.usc.edu
Xiong
S
S
Felix
J
J
Roda
N
N
Espinoza
T
T
Maldonado
S
S
Dizerega
G
G
D000803:Angiotensin I / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000627:therapeutic use; D000818:Animals; D001706:Biopsy; D048909:Diabetes Complications; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)