In vitro and in vivo studies of homocysteine in equine tissues: Implications for the pathophysiology of laminitis

Abstract

Reasons for performing study: 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. Hypothesis: HCy causes dysfunction of equine vascular endothelium and elevated plasma concentrations predispose to laminitis. Objectives: 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 μmol/l) inhibited endothelial function and, at concentrations above 100 μmol/l, inhibited NO production by EDVECs. Plasma tHCy concentration ranged from 1.3 to 14.7 μmol/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. Potential relevance: 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.