Plastic Surgery Research Council
Members Only  |  Contact  |  PSRC on Facebook

Back to Annual Meeting Program


LOSARTAN AND TREATMENT OF SCAR CONTRACTURE: PRECLINICAL STUDIES INTO THE ROLE OF ANGIOTENSIN, ITS RECEPTORS AND EFFECT ON ACTIN ISOFORM EXPRESSION IN SCAR CONTRACTURE.
Presenter: Jennifer Bond, PhD
Co-Authors: Ehanire T; Ren L; Levinson H
Duke University Medical Center

Following dermal injury, the subsequently formed scar can progressively shorten and form a contracture. Scar contracture limits range of motion and interferes with daily living, Contracture is mediated by fibroblast migration and contractility that leads to tissue contraction. Here we study the role of angiotensin II (AngII) and its receptors ATr1 and ATr2 in contracture by using human tissue, in vivo model of contraction, and in vitro primary human fibroblast assays. Human scar tissue and surrounding normal tissue were stained for ATr1 and ATr2. ATr1 expression was increased in human scar dermal tissue compared to normal which did not express ATr1. Wounds were created on the dorsum of wild type (WT) and alpha smooth muscle actin knockout (ASMA, KO) treated with Losartan (50mg/kg/d) or AngII (3mg/kg/d) and allowed to contract. Losartan inhibited contraction significantly by >40%. Administering exogenous AngII resulted in expedited contraction in both treated and untreated groups at equal rates without significant difference between KO and WT. AngII had no effect on actin isoform expression. AngII stimulated human fibroblast contraction (fibroblast population collagen lattice) and migration (boyden chambers) in a dose-dependent manner and was inhibited by ATr1 and not ATr2 antagonism. AngII increased non muscle myosin, and alpha- beta-, gamma- and F- actin expression. These data suggest AngII signaling through ATr1 is a target to prevent scar contracture. Surprisingly, in vivo this effect was achieved independent of ASMA expression which is traditionally thought to be the contractile protein involved in contracture. Future work includes the study of AngII/ATr1 inhibitors in alternative models and mechanistic studies to determine how AngII mediates fibroblast contractility through G-protein independent/dependent signaling and different isoforms of actins.


Back to Annual Meeting Program