Evidence for vascular and enzymatic events in the pathophysiology of acute laminitis: which pathway is responsible for initiation of this process in horses?
Authors: Moore, Eades, Stokes
Journal: Equine veterinary journal
Summary
# Editorial Summary: Vascular and Enzymatic Pathways in Acute Laminitis Moore, Eades and Stokes (2004) examined whether vascular dysfunction or enzymatic degradation drives the initiation of acute laminitis, reviewing experimental evidence for both mechanisms alongside clinical observations. Whilst substantial in vitro data support both theories—showing vascular changes and matrix metalloproteinase (MMP) activity compromising dermo-epidermal attachments—the authors highlight a critical gap: neither vascular antagonists nor MMP inhibitors have successfully prevented or reversed laminitis in vivo, suggesting these pathways alone are insufficient. The evidence points instead towards simultaneous activation of multiple inflammatory cascades, with common mediators like interleukin-1β capable of triggering both vasoactive responses and enzymatic activity concurrently, alongside mechanical factors that remain poorly characterised. The variable presentation of naturally acquired laminitis and the well-recognised phenomenon of contralateral limb involvement following unilateral weight-bearing disease underscore the likelihood of multiple initiating mechanisms. For practitioners, this implies that successful management requires multimodal intervention rather than reliance on single-target therapeutics, and highlights the importance of addressing underlying predisposing conditions alongside direct laminar support.
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Practical Takeaways
- •Single-target treatments addressing only vascular or enzymatic pathways are unlikely to be effective—clinicians should anticipate the need for combined therapeutic strategies in laminitis management
- •Contralateral limb laminitis in weight-bearing disease suggests systemic inflammatory activation rather than purely local vascular or mechanical mechanisms, supporting systemic anti-inflammatory protocols
- •The variable presentation and severity of naturally acquired laminitis across different predisposing conditions indicates that successful treatment will require individualized, multi-modal approaches tailored to the underlying cause
Key Findings
- •Substantial evidence supports both vascular and enzymatic pathways in acute laminitis, but neither has been definitively proven as the sole initiating mechanism in vivo
- •MMP inhibitors and vasoactive antagonists have failed to prevent or reverse laminitis-induced pathophysiological changes, suggesting single-pathway intervention is insufficient
- •Multiple inflammatory mediators including interleukin-1beta can simultaneously activate both vascular and enzymatic cascades, supporting a concurrent multi-pathway model
- •Naturally acquired laminitis shows variable severity across predisposing diseases, indicating multiple mechanisms of initiation and propagation requiring multi-modal treatment approaches