Chemotherapy and radiation regimens to breast cancer treatment induce changes in mRNA levels of renin-angiotensin system related genes in cardiac tissue

J Renin Angiotensin Aldosterone Syst. 2013 Dec;14(4):330-6. doi: 10.1177/1470320312465218. Epub 2012 Nov 6.

Abstract

Background and aim: Cardiovascular complications are one limitation of breast cancer treatment. The aim of the current study was to investigate whether the renin-angiotensin related genes could be altered by chemotherapy and radiotherapy, using a rat model.

Methods: Female rats were divided into three groups: control, chemotherapy + irradiation (TC+IR) and irradiation (IR). Molecular analyses of the left ventricle were performed five months after the end of treatment. The analyses evaluated the changes in mRNA levels of some renin-angiotensin system (RAS) related genes: angiotensinogen, renin, angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1) and vascular endothelial growth factor (VEGF), which can be related to ACE production, by RT-PCR.

Results: Renin was only observed in treated groups, TC+IR and IR, compared with the control group. ACE and VEGF levels were decreased in TC+IR (p<0.001) and in IR (p<0.001), and AT1 mRNA was higher in groups TC+IR (p<0.01) and IR (p<0.05) compared with the control group.

Conclusion: Chemotherapy and irradiation can induce significant changes in some RAS related genes. These alterations are important to understand the pathways and consequences beyond cardiotoxicity induced by breast cancer treatments.

Keywords: Breast cancer; RAS; cardiotoxicity; chemotherapy; radiotherapy.

MeSH terms

  • Angiotensinogen / genetics
  • Angiotensinogen / metabolism
  • Animals
  • Female
  • Gene Expression Regulation*
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / radiotherapy*
  • Mast Cells / metabolism
  • Myocardium / metabolism*
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Renin / genetics
  • Renin / metabolism
  • Renin-Angiotensin System / genetics*
  • Staining and Labeling
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Vascular Endothelial Growth Factor A
  • Angiotensinogen
  • Peptidyl-Dipeptidase A
  • Renin