In vitro and in vivo studies of homocysteine in equine tissues: implications for the pathophysiology of laminitis.
BACKGROUND
Elevated plasma homocysteine (HCy) concentration is a risk factor for cardiovascular diseases associated with endothelial dysfunction, including the human digital ischaemic disease, Raynaud's phenomenon.


OBJECTIVE
HCy causes dysfunction of equine vascular endothelium and elevated plasma concentrations predispose to laminitis.


OBJECTIVE
To determine 1) the concentration of HCy in vitro, which inhibits equine vascular endothelial cell function and 2) any association between risk of laminitis and plasma HCy concentration.


METHODS
Endothelial function was studied by measuring endothelium-dependent vasodilatory responses of the equine isolated perfused digit and basal nitric oxide (NO) production by cultured equine digital vein endothelial cells (EDVECs). Total plasma HCy (tHCy) concentrations were measured in samples collected in the winter and spring from normal ponies and ponies predisposed to laminitis.


RESULTS
HCy (10 and 100 micromol/l) inhibited endothelial function and, at concentrations above 100 micromol/l, inhibited NO production by EDVECs. Plasma tHCy concentration ranged from 13 to 14.7 micromol/l. There was no effect of season or disease status on the concentration measured.


CONCLUSIONS
In vitro, HCy was shown to interfere with endothelial cell function at physiologically relevant concentrations. No evidence was found for an association between risk of laminitis and high plasma concentrations of HCy.


CONCLUSIONS
Elevated plasma HCy concentrations could adversely affect endothelial cell function and mangement regimens that lead to increases in plasma HCy concentration should be avoided in ponies predisposed to laminitis.
Berhane
Y
Y
Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
Bailey
S R
SR
Harris
P A
PA
Griffiths
M J
MJ
Elliott
J
J
D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D006152:Cyclic GMP / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005534:Foot Diseases / Q000453:epidemiology / Q000378:metabolism / Q000662:veterinary*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D006724:Hoof and Claw / Q000098:blood supply*; D006734:Horse Diseases / Q000453:epidemiology / Q000378:metabolism*; D006736:Horses; D007249:Inflammation / Q000453:epidemiology / Q000378:metabolism / Q000662:veterinary; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D012307:Risk Factors; D012621:Seasons; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D006710:Homocysteine; D009569:Nitric Oxide; D006152:Cyclic GMP