Shahnaz Shekarforoush1, Farhad Koohpeyma2, Fatemeh Safari3,4. 1. a Department of Physiology , Arsanjan Branch, Islamic Azad University , Fars , Iran. 2. b Endocrine and Metabolism research center , Shiraz University of Medical Sciences , Shiraz , Iran. 3. c Biotechnology Research Center, International Campus , Shahid Sadoughi University of Medical Sciences , Yazd , Iran. 4. d Department of Physiology, Faculty of Medicine , Shahid Sadoughi University of Medical Sciences , Yazd , Iran.
Abstract
INTRODUCTION: The use of aromatase inhibitors (AIs) for breast cancer led to a marked change in ventricular function. Since accumulating evidence indicates that overactivation of the cardiac renin-angiotensin system (RAS) plays an important role in the development of cardiovascular diseases such as hypertrophy and remodelling, we aimed to investigate whether letrozole alters the transcription level of RAS related genes in the cardiac tissue. METHODS: Twenty four rats were randomly divided into four groups (n = 6 per group): two groups were letrozole treated (1 and 2 mg/kg/day orally), one group was vehicle treated (DMSO) and one group was the control group without any treatment. 12 weeks after beginning treatment with letrozole, we examined the rate of transcription of renin, angiotensinogen, AngII type 1a and 1b (AT1a and AT1b) and type 2 receptors (AT2) in the rat heart using real-time polymerase chain reaction. RESULTS: The cardiac mRNA levels of several components of the RAS in the rats treated with letrozole were significantly increased including AT1a receptor (80%), renin (51%), and angiotensinogen (33%). Though not significant, AT2 receptor levels were observed to decrease with increasing doses of letrozole. CONCLUSIONS: Letrozole can induce significant changes in some RAS related genes. These alterations are important to understand the pathways and consequences beyond cardiac events induced by breast cancer treatments.
INTRODUCTION: The use of aromatase inhibitors (AIs) for breast cancer led to a marked change in ventricular function. Since accumulating evidence indicates that overactivation of the cardiac renin-angiotensin system (RAS) plays an important role in the development of cardiovascular diseases such as hypertrophy and remodelling, we aimed to investigate whether letrozole alters the transcription level of RAS related genes in the cardiac tissue. METHODS: Twenty four rats were randomly divided into four groups (n = 6 per group): two groups were letrozole treated (1 and 2 mg/kg/day orally), one group was vehicle treated (DMSO) and one group was the control group without any treatment. 12 weeks after beginning treatment with letrozole, we examined the rate of transcription of renin, angiotensinogen, AngII type 1a and 1b (AT1a and AT1b) and type 2 receptors (AT2) in the rat heart using real-time polymerase chain reaction. RESULTS: The cardiac mRNA levels of several components of the RAS in the rats treated with letrozole were significantly increased including AT1a receptor (80%), renin (51%), and angiotensinogen (33%). Though not significant, AT2 receptor levels were observed to decrease with increasing doses of letrozole. CONCLUSIONS:Letrozole can induce significant changes in some RAS related genes. These alterations are important to understand the pathways and consequences beyond cardiac events induced by breast cancer treatments.
Entities:
Keywords:
Renin-Angiotensin system; breast cancer; cardiac disease; gene Transcription; letrozole