A review of cellular and molecular mechanisms in endocrinopathic, sepsis‐related and supporting limb equine laminitis

Equine laminitis has both fascinated and frustrated veterinary researchers and clinicians for many years. The recognition that many ponies suffering from pasture-associated laminitis have an insulin-dysregulated phenotype (endocrinopathic laminitis, EL) and that prolonged insulin and glucose infusions can experimentally induce laminar pathology and functional failure are seminal discoveries in this field. Researchers have studied the molecular basis for disease pathogenesis in models of EL, sepsis-related laminitis and supporting limb laminitis and generated much data over the last 15 years. This review attempts to synthesise those data, drawing comparisons between models and naturally occurring laminitis. A hypothesis is proposed that the basal epithelial cell stress is a central event in each category of laminitis. Furthermore, in naturally occurring pasture-associated laminitis, pathways that predominate in each type of laminitis contribute to laminar lamellar pathology to varying extents. Based on the molecular mechanisms determined in experimental models, interactions between these pathways are identified.