Heart rate reduction with ivabradine in the early phase of atherosclerosis is protective in the endothelium of ApoE-deficient mice

Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society
G AquilaP Rizzo

Abstract

Ivabradine, a heart rate reducing agent, protects the vascular system by unidentified mechanisms. We 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. Microarrays analysis (60k probes) of endothelium-enriched RNA was carried out to detect changes in gene expression induced by treatment. Endothelium damage was assessed by en-face immunofluorescence staining for vascular endothelial (VE) cadherin. According to microarray analysis, 930 transcripts were affected by the treatment. We found downregulation of pro-apoptotic and pro-inflammatory genes, the majority of which are nuclear factor-κB (NF-κB)-and/or angiotensin II-regulated genes, and upregulation of anti-inflammatory genes. Many shear stress-responsive genes were affected by the treatment and the MAPK, Notch signalling and sterol metabolic processes were am...Continue Reading

Citations

Jun 14, 2019·Frontiers in Immunology·Francesco Vieceli Dalla SegaPaola Rizzo
Jan 10, 2020·Oxidative Medicine and Cellular Longevity·Giorgio AquilaPaola Rizzo
Oct 9, 2019·International Journal of Molecular Sciences·Francesco Vieceli Dalla SegaSaverio Francesco Retta
Mar 2, 2021·Frontiers in Cardiovascular Medicine·Fedor Simko, Tomas Baka
Aug 28, 2021·Biomedicines·Francesca FortiniRoberto Ferrari

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