Localization of the Renin-Angiotensin System in the Bovine Ovary: Cyclic Variation of the Angiotensin II Receptor Expression1

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.

Download Full-text

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

Lung Cancer International ◽

10.1155/2017/6914976 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Benjamin Goldstein ◽

Malav Trivedi ◽

Robert C. Speth

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

System Component ◽

Receptor Subtype ◽

Angiotensin Ii Receptor ◽

Statistical Tool ◽

Tissue Samples ◽

Angiotensin System ◽

Lung Cancers ◽

Renin Angiotensin

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.

Download Full-text

Molecular Genetics of the Renin-Angiotensin System: Implications for Angiotensin II Receptor Blockade

Pharmacology & Therapeutics ◽

10.1016/s0163-7258(97)00021-1 ◽

1997 ◽

Vol 75 (1) ◽

pp. 43-50 ◽

Cited By ~ 24

Author(s):

Gershan K Davis ◽

David H Roberts

Keyword(s):

Angiotensin Ii ◽

Molecular Genetics ◽

Renin Angiotensin System ◽

Receptor Blockade ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Renin Angiotensin ◽

Angiotensin Ii Receptor Blockade

Download Full-text

Angiotensin II receptor blockade in TGR(mREN2)27: effects of renin???angiotensin-system gene expression and cardiovascular functions

Journal of Hypertension ◽

10.1097/00004872-199508000-00010 ◽

1995 ◽

Vol 13 (8) ◽

pp. 891-899 ◽

Cited By ~ 68

Author(s):

Manfred B??hm ◽

MinAe Lee ◽

Reinhold Kreutz ◽

Shokei Kim ◽

Martina Schinke ◽

...

Keyword(s):

Gene Expression ◽

Angiotensin Ii ◽

Renin Angiotensin System ◽

Receptor Blockade ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Renin Angiotensin ◽

Angiotensin Ii Receptor Blockade ◽

Cardiovascular Functions

Download Full-text

Inhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury

Journal of the American Society of Nephrology ◽

10.1681/asn.2019010053 ◽

2019 ◽

Vol 30 (12) ◽

pp. 2307-2320 ◽

Cited By ~ 4

Author(s):

Kazunori Inoue ◽

Xuefei Tian ◽

Heino Velazquez ◽

Keita Soda ◽

Zhen Wang ◽

...

Keyword(s):

Angiotensin Ii ◽

Knockout Mice ◽

Renin Angiotensin System ◽

Membrane Dynamics ◽

Receptor Type ◽

Angiotensin Ii Receptor ◽

Double Knockout ◽

Angiotensin System ◽

Renin Angiotensin

BackgroundInhibition of the renin-angiotensin system remains a cornerstone in reducing proteinuria and progression of kidney failure, effects believed to be the result of reduction in BP and glomerular hyperfiltration. However, studies have yielded conflicting results on whether podocyte-specific angiotensin II (AngII) signaling directly induces podocyte injury. Previous research has found that after AngII stimulation, β-arrestin–bound angiotensin II receptor type 1 (AT1R) is internalized in a clathrin- and dynamin-dependent manner, and that Dynamin1 and Dynamin2 double-knockout mice exhibit impaired clathrin-mediated endocytosis.MethodsWe used podocyte-specific Dyn double-knockout mice to examine AngII-stimulated AT1R internalization and signaling in primary podocytes and controls. We also examined the in vivo effect of AngII in these double-knockout mice through renin-angiotensin system blockers and through deletion of Agtr1a (which encodes the predominant AT1R isoform expressed in kidney, AT1aR). We tested calcium influx, Rac1 activation, and lamellipodial extension in control and primary podocytes of Dnm double-knockout mice treated with AngII.ResultsWe confirmed augmented AngII-stimulated AT1R signaling in primary Dnm double-knockout podocytes resulting from arrest of clathrin-coated pit turnover. Genetic ablation of podocyte Agtr1a in Dnm double-knockout mice demonstrated improved albuminuria and kidney function compared with the double-knockout mice. Isolation of podocytes from Dnm double-knockout mice revealed abnormal membrane dynamics, with increased Rac1 activation and lamellipodial extension, which was attenuated in Dnm double-knockout podocytes lacking AT1aR.ConclusionsOur results indicate that inhibiting aberrant podocyte-associated AT1aR signaling pathways has a protective effect in maintaining the integrity of the glomerular filtration barrier.

Download Full-text