Species-specific regulation of angiogenesis by glucocorticoids reveals contrasting effects on inflammatory and angiogenic pathways.
Authors: Morgan Ruth, Keen John, Halligan Daniel, O'Callaghan Alan, Andrew Ruth, Livingstone Dawn, Abernethie Amber, Maltese Giorgia, Walker Brian, Hadoke Patrick
Journal: PloS one
Summary
# Editorial Summary Glucocorticoids are routinely administered in equine practice to manage inflammation, yet their effects on blood vessel growth remain poorly understood—particularly in horses, where extrapolation from rodent research may be misleading. Researchers adapted the mouse aortic ring model to directly compare how cortisol affects angiogenesis in equine versus murine vessels, exposing cultured vessel rings to cortisol (600 nM) with and without growth factors, glucocorticoid receptor antagonists, or mineralocorticoid antagonists. Whilst cortisol suppressed new vessel formation in mice, it paradoxically stimulated robust angiogenic responses in equine blood vessels through glucocorticoid receptor-mediated signalling; transcriptomic analysis revealed that cortisol suppressed inflammatory pathways in both species but selectively upregulated pro-angiogenic and extracellular matrix pathways only in horses. These findings suggest that glucocorticoids may promote tissue healing and vascular remodelling in equine patients—a marked departure from rodent biology—with potentially important implications for clinical conditions where angiogenesis supports repair, such as tendon and ligament injuries, whilst also raising questions about optimal dosing and duration of glucocorticoid therapy in managing inflammatory conditions where excessive angiogenesis might be undesirable.
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Practical Takeaways
- •Glucocorticoid administration in horses may have fundamentally different vascular effects than predicted from rodent studies—potentially promoting rather than inhibiting new blood vessel formation.
- •When using glucocorticoids therapeutically in horses, clinicians should reconsider assumptions about angiostatic effects and evaluate whether enhanced angiogenesis could be beneficial or detrimental to specific conditions.
- •Species-specific differences in glucocorticoid response underscore the importance of equine-specific research when extrapolating drug effects from laboratory animal models to clinical practice.
Key Findings
- •Cortisol inhibited angiogenesis in murine aortic rings but stimulated new vessel growth in equine blood vessels, demonstrating species-specific glucocorticoid effects.
- •The pro-angiogenic response in equine vessels to cortisol was mediated through glucocorticoid receptor antagonism but not mineralocorticoid receptor antagonism.
- •Cortisol down-regulated inflammatory pathways in both species but selectively up-regulated pro-angiogenic pathways only in equine vessels.
- •Extracellular matrix genes were up-regulated in horse and down-regulated in mice in response to cortisol, suggesting species-specific vascular remodeling mechanisms.