The antiangiogenic effects of levosimendan in a CAM assay

There is a physiological balance between the stimulatory and inhibitory signals for blood vessel growth. In many symptomatic patients with peripheral artery disease, coronary artery disease, and ischemic chronic wounds, there is a pathological insufficiency of angiogenesis. Therefore, determining the angiogenic or antiangiogenic effects of molecules currently used in cardiovascular treatment is crucial. Although levosimendan is the most well studied calcium sensitizer in preclinical and clinical practice, to the best of our knowledge, there are no previous studies investigating its angiogenic or antiangiogenic effects. In the present study, we aimed to investigate the effects of levosimendan on angiogenesis.

The antiangiogenic efficacy of levosimendan was examined in vivo in the chick chorioallantoic membrane (CAM) model by using 20 fertilized eggs and drug solutions of 1 and 10 μmol/L concentrations. Decreases in the density of the capillaries were assessed and scored.

Significant antiangiogenic effects were observed at 1 and 10 μmol/L concentrations of levosimendan. The antiangiogenic scores of levosimendan at 1 and 10 μmol/L concentrations were 0.6 and 1.10, respectively. The antiangiogenic score of bevacizumab, used as a positive control, was 0.95 at 1.0 μmol/L concentration. No significant difference was found between the antiangiogenic scores of levosimendan and bevacizumab (p=0.54).

Our results indicate that levosimendan has antiangiogenic effects on the chorioallantoic membrane. However, these findings must be confirmed in future studies on humans.