Comparative study on microvascular occlusion and apoptosis in body and limb wounds in the horse

Abstract

Wound repair in horse limbs is often complicated by exuberant granulation tissue, a condition characterized by excessive fibroplasia and scarring and that resembles hypertrophic scars and keloids in man. The aim of this study was to compare microvascular occlusion and apoptosis in wounds of the limb with those of the body, which heal normally. Five 6.25 cm(2) wounds were created on both forelimbs and on the body of six horses. One limb was bandaged to stimulate excessive fibroplasia. Weekly biopsies were evaluated histologically and immunohistochemically for mutant p53 protein by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling to localize and quantify apoptosis, and by electron microscopy to measure microvessel luminal diameters. Histologic examination revealed protracted inflammation as well as slowed epithelialization and deficient fibroblast orientation in limb wounds, particularly those with excessive fibroplasia. Microvessels were occluded significantly more often in limb wounds, and the balance of apoptotic signals was altered against apoptosis in the former, although this could not be confirmed quantitatively. Data suggest that microvascular occlusion and a dysregulated apoptotic process may be involved in the excessive accumulation of extracellular matrix within limb wounds. This might provide a basis for the development of targeted therapies to prevent and treat excessive fibroplasia and extensive scarring in horses.