Histomorphometric Features of the Common Carotid Artery of Albino Rats (Rattus Norvegicus Domesticus) Following Letrozole Administration

Abstract

Background Aromatase inhibitors (AIs) such as letrozole are used in treatment of hormone-responsive breast cancer by reducing levels of circulating estrogen. Their use has been associated with adverse cardiovascular events including myocardial infarction and stroke. Although their effect on the structure of blood vessels remains unexplored, their atherogenic potential has been demonstrated sonographically by presence of atheromatous plaques in the common carotid arteries of patients on treatment with AIs. The structural changes that underlie this are yet to be demonstrated. This study therefore sought to describe the structural effect of letrozole on the common carotid arteries. Broad objective: To describe the histomorphometric features of the common carotid artery following letrozole administration. Research question: What are the histomorphometric features of the common carotid artery following letrozole administration? Study type: Quasi-experimental study Methods: Twenty-seven male rats (3 baseline, 15 experimental, 9 control) aged three months were used for the study. The experimental group received 0.5 mg/kg of letrozole dissolved in distilled water daily by oral gavage while the control group received 2 ml of normal saline daily by oral gavage as placebo. The rats were randomly selected, euthanized, perfused and their carotid arteries harvested for histological processing on days 20, 35 and 50. Stereological techniques were used to determine the densities of different histological components. Data were analyzed using the statistical package for social sciences (SPSS V25, Chicago, Illinois). Results are presented in photomicrographs, tables and graphs. Results: In response to letrozole administration, statistically significant temporal increases in carotid intima-medial thickness (p=0.002), collagen fiber density (p<0.0001), and vascular smooth muscle cell density (p <0.001) were noted. Adventitial thickness also increased albeit not statistically significant (p=0.09). Elastic fiber organization also displayed disruption with branching of elastic lamellae and fragmentation, and a reduction in elastic fiber density (p=0.009) 12 Conclusion: Letrozole administration is associated with increased carotid intima-medial thickness, vascular smooth muscle density and collagen fiber density and reduced elastic fiber density. These changes could affect the function of the vessel wall and may explain the greater incidence of cardiovascular disease in patients taking aromatase inhibitors