Effect of experimentally induced mitral regurgitation on endothelial cell-specific molecule-1 as a biomarker of endothelial injury in dogs.

Objective: To investigate changes in plasma endothelial cell-specific molecule-1 (ESM-1) concentrations following mitral regurgitation (MR) induction in dogs and to evaluate their association with established diagnostic markers of myxomatous mitral valve disease.

Methods: Purpose-bred Beagles were enrolled in a prospective, nonrandomized, controlled trial from January 2024 through March 2025. Mitral regurgitation was induced in each dog via a minimally invasive intervention under fluoroscopic guidance with mean left atrial pressure monitoring. Plasma ESM-1 concentrations were measured at baseline, 30 minutes postoperatively (PO), and 6 weeks PO. Plasma atrial natriuretic peptide concentrations and hemodynamic, radiographic, and echocardiographic variables were evaluated at baseline and 6 weeks PO.

Results: All 6 Beagles enrolled in the study developed pathological MR without clinical signs. Their plasma ESM-1 concentrations significantly increased at 6 weeks PO from the baseline, whereas no significant change was observed at 30 minutes PO. The ESM-1 concentration was positively correlated with the left atrial-to-aortic diameter ratio, peak early diastolic transmitral velocity, and early diastolic transmitral velocity-to-early diastolic mitral annular velocity. No significant correlations were found for other variables.

Conclusions: Experimentally induced MR led to a delayed but significant increase in plasma ESM-1 concentrations, which were positively associated with echocardiographic indicators of diastolic dysfunction and left atrial volume overload. Endothelial cell-specific molecule-1 expression and acute mean left atrial pressure elevation were not associated.

Clinical Relevance: Plasma ESM-1 concentrations may reflect early endothelial glycocalyx degradation during the asymptomatic stages of myxomatous mitral valve disease and represent a potential endothelial injury biomarker in veterinary cardiology.