HMG-CoA reductase inhibitors (statins) reduce hypertrophic scar formation in a rabbit ear wounding model

Background: 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, also known as statins, are the most commonly prescribed cholesterol-lowering medications in the world. Statins have been shown to inhibit connective tissue growth factor (CTGF) gene and protein expression in vitro, and previous studies in the authors' laboratory have demonstrated that CTGF plays a significant role in wound healing and scarring. The authors explore whether administration of various statins to healing wounds has any effect on hypertrophic scar formation using an established rabbit ear wounding model. Methods: Punch wounds were made on the ears of 31 rabbits (n = 372 total wounds). Treatment wounds were injected with simvastatin, lovastatin, or pravastatin at low, medium, or high doses on postwounding days 15, 20, and 25, whereas control wounds were injected in a corresponding fashion. Wounds were harvested after 35 days for histomorphometric analysis. Results: Low-dose (40 μM) simvastatin, lovastatin, and pravastatin each demonstrated significant reductions in scar elevation index when compared with control: 21.9 percent (p = 0.03), 25.8 percent (p = 0.02), and 22.8 percent (p = 0.01), respectively. There were no significant differences in scar elevation index in the medium- (120 μM) and high-dose (400 μM) statin groups. Analysis of mRNA in a subset of rabbits treated with low-dose simvastatin demonstrated a significant reduction in CTGF expression (p = 0.009). Conclusions: 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors reduce hypertrophic scar formation by means of CTGF inhibition when administered at low doses, and the novel application of these commonly prescribed medications may lead to innovative and effective antiscarring therapies.