scholarly journals Alterations in Gene Expression of Components of the Renin-Angiotensin System and Its Related Enzymes in Lung Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Benjamin Goldstein ◽  
Malav Trivedi ◽  
Robert C. Speth

Objectives. The study assessed the existence and significance of associations between the expression of fifteen renin-angiotensin system component genes and lung adenocarcinoma. Materials and Methods. NCBI’s built-in statistical tool, GEO2R, was used to calculate Student’s t-tests for the associations found in a DNA expression study of adenocarcinoma and matched healthy lung tissue samples. The raw data was processed with GeneSpring™ and then used to generate figures with and without Sidak’s multiple comparison correction. Results. Ten genes were found to be significantly associated with adenocarcinoma. Seven of these associations remained statistically significant after correction for multiple comparisons. Notably, AGTR2, which encodes the AT2 angiotensin II receptor subtype, was significantly underexpressed in adenocarcinoma tissue (p<0.01). AGTR1, ACE, ENPEP, MME, and PRCP, which encode the AT1 angiotensin II receptor, angiotensin-converting enzyme, aminopeptidase N, neprilysin, and prolylcarboxypeptidase, respectively, were also underexpressed. AGT, which encodes angiotensinogen, the angiotensin peptide precursor, was overexpressed in adenocarcinoma tissue. Conclusion. The results suggest an association between the expression of the genes for renin-angiotensin system-related proteins and adenocarcinoma. While further research is necessary to conclusively demonstrate a link between the renin-angiotensin system and lung cancers, the results suggest that the renin-angiotensin system plays a role in the pathology of adenocarcinoma.

2001 ◽  
Vol 120 (5) ◽  
pp. A313-A314
Author(s):  
Koki Hirasawa ◽  
Yoshihiko Sato ◽  
Yoshisuke Hosoda ◽  
Tatsuo Yamamoto ◽  
Hiroyuki Hanai

2018 ◽  
Vol 6 (6) ◽  
pp. 955-960 ◽  
Author(s):  
Sameh Saber ◽  
Amr Mahmoud ◽  
Noha Helal ◽  
Eman El-Ahwany ◽  
Rasha Abdelghany

BACKGROUND: Preclinical studies have demonstrated that renin-angiotensin system (RAS) signalling has strong tumour-promoting effects and RAS inhibition was associated with improvement in the overall survival in some cancer types including hepatocellular carcinoma (HCC).OBJECTIVE: We aimed to investigate the effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) on the survival of mice with diethylnitrosamine (DEN) induced HCC.METHODS: HCC was induced by weekly i.p. administration of DEN. Mice were treated with sorafenib (SO) (30 mg/kg), perindopril (PE) (1 mg/kg), fosinopril (FO) (2 mg/kg), losartan (LO) (10 mg/kg), PE (1 mg/kg) + SO (30 mg/kg), FO (2 mg/kg) + SO (30 mg/kg), or LO (10 mg/kg) + SO (30 mg/kg). Survival analysis was done using the Kaplan-Meier method, and the log-rank test was used for assessing the significance of difference between groups.RESULTS: The administration of PE, FO and LO as monotherapy or as combined with SO resulted in marked improvement in the liver histologic picture with no impact on overall survival of mice.CONCLUSION: Interfering the RAS either through the inhibition of ACE or the blockade of angiotensin II type 1 (AT1) receptors has similar effects on the liver of DEN-induced HCC mice and is not associated with longer survival due to detrimental effects of DEN on other organs. Hence, repetitive administration of DEN in such models of HCC is not suitable for mortality assessment studies.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Domenig Oliver ◽  
Arndt Manzel ◽  
Johannes Stegbauer ◽  
Susan B Gurley ◽  
Marlies Antlanger ◽  
...  

The Renin-Angiotensin-System is a peptide hormone cascade being responsible for the regulation of blood pressure and fluid balance through a sophisticated signaling network. During recent years the local Renin-Angiotensin-System (RAS) moved increasingly into the focus of research as the expression of multiple angiotensin processing enzymes had been reported for tissues. Nevertheless, scientific progress in this field is hampered due to the obvious presence of technical caveats in the analysis of the local RAS, which are indicated by a tremendous variation of tissue angiotensin levels reported in the literature. Hence, in order to assess the functions of the local RAS in different tissues, a solid and reproducible assay for the measurement of endogenous angiotensin peptide levels in tissues would be essential. We developed a novel mass-spectrometry-based method allowing the quantification of up to 10 angiotensin metabolites in tissue samples simultaneously. This novel tool was tested for applicability in murine studies by measuring tissue and plasma levels of angiotensin metabolites in wildtype and ACE2 knockout mice treated with various RAS-interfering drugs. The study provided deep insights into the systemic and tissue specific RAS revealing drug specific responses. As expected, the knockout of ACE2 resulted in increased Angiotensin II levels in hearts of knockout animals while the kidneys were only moderately affected. Enalapril treatment significantly lowered Angiotensin II levels in all investigated tissues. Surprising tissue specific effects were observed regarding other angiotensin metabolites, which underlines the importance of the comprehensive analysis of the RAS for conclusive interpretation of pharmacologic studies and allows to draw conclusions about expression levels of RAS-enzymes in the tissue of interest. Mass spectrometry based multiplex quantification of tissue angiotensin peptides (Tissue RAS-Fingerprinting) is a potent analytic tool for applications in basic science and drug development. Multiplex analysis of the tissue RAS provides new insights that might lead to the development of novel drugs and therapeutic concepts for the treatment of cardiovascular diseases in the future.


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