Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Angiotensin Receptor Blockade is Associated with Decreased Cutaneous Scar Formation in a Rat Model: A Preclinical Study
Amanda M. Murphy, MD, Michael Bezuhly, MD, MSc, SM, FRCSC, Simon Gebremeskel, BSc, Terry LeVatte, BA, Paul Gratzer, PhD.
Dalhousie University, Halifax, NS, Canada.

PURPOSE
Local production of angiotensin II (AngII) following injury has been linked to fibrosis in a variety of non-cutaneous tissues via AngII type 1 receptor (AT1R)-dependent up-regulation of TGF-β. Angiotensin receptor blockers (ARB) are widely used clinically and attenuate TGF-β overexpression and collagen deposition in numerous fibro-inflammatory conditions. Both AngII receptors and TGF-β expression are increased in hypertrophic scars; however, the effect of AT1R blockade in cutaneous scarring has not been directly examined. Our aim was to evaluate the effect of the ARB losartan on hypertrophic scar development.
METHODS
Hypertrophic scars were generated on the backs of 12 Sprague-Dawley rats using a mechanical distraction model. Animals received oral losartan (0.3mg/kg/d) or control vehicle over the distraction period. Scar tissue was collected at 4 weeks and evaluated histologically for scar area and scar elevation index (SEI). Immunohistochemistry was performed for the presence of inflammatory cells and myofibroblasts. Messenger RNA and protein expression of Smads 2/3, TGF-β, α-smooth muscle actin, and collagens I and III were evaluated. The effect of losartan on human dermal fibroblast (HDF) contractile, migratory and synthetic functions was assessed in vitro.
RESULTS
Mechanical distraction increased scar deposition in all animals. Losartan treatment was associated with decreased scar area and SEI (p<0.05). Additionally, dermal appendages, characteristically absent in hypertrophic scars, were present in losartan-treated, but not control, animals. Immunohistochemical analysis revealed a decreased density of inflammatory cells and myofibroblasts in losartan-treated specimens. Losartan treatment decreased HDF migration and contractile function following scratch assay (p<0.05) and collagen contraction assay (mean gel contraction 79.40 ± 14.31 vs. 19.52 ± 8.6, p=0.001) respectively.
CONCLUSIONS
Our results suggest that AngII plays an important role in the development of hypertrophic scars. Inhibition of the AT1R with losartan resulted in decreased cutaneous scar formation and inhibited fibroblast migration and contractile function in vitro.


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