Epidemiological studies have shown that elevated heart rate (HR) is a marker of coronary artery disease (CAD) progression and correlates with cardiovascular mortality. In accordance, experimental data suggest that reduction in resting HR slows endothelial cell (EC) replication, a marker of endothelial dysfunction, and reduces the progression of atherosclerosis in the cynomolgus monkeys fed a high fat diet.
Ivabradine, a heart rate reducing agent, protects the vascular system by unidentified mechanisms. Based on this background, the Authors of this paper sought to determine the effects of the treatment with ivabradine, started before plaque formation, on early transcriptional changes and endothelium lesions in regions of aorta subjected to disturbed blood flow.
Six week-old apolipoprotein E-deficient (ApoE-/-) mice, fed a low-fat diet, were treated with ivabradine to determine the effect on transcriptional changes (2-and 4-week treatment) and on lesions formation (19-week treatment) in the endothelium of the aortic arch.
According to the conclusions, an early treatment with ivabradine actually protected the endothelium of the aortic arch of ApoE–/– mice. Activation of the Notch signalling could be part of the mechanism underlying this protection.