Role of transcriptional cis-elements, angiotensinogen gene-activating elements, of angiotensinogen gene in blood pressure regulation

Hypertension
Ryuichi MorishitaToshio Ogihara

Abstract

Results of recent genetic studies suggest that the angiotensinogen gene is a possible determinant of hypertension. Using antisense technology, we demonstrated that generation of circulating angiotensinogen is a rate-limiting step in blood pressure regulation. In the present study, we examined how the angiotensinogen gene is regulated in vivo. The transcriptional cis-elements, angiotensinogen gene-activating elements (AGE) 2 and 3, have been reported to regulate angiotensinogen production in human hepatocytes in vitro. To determine the critical transcriptional regulator of angiotensinogen production in vivo, we used synthetic double-stranded oligodeoxynucleotides (ODN) as "decoy" cis-elements to block the binding of nuclear factors to promoter regions of the targeted gene, resulting in the inhibition of gene transactivation. Here we examined whether AGE 2 and AGE 3 in the promoter region of the angiotensinogen gene have a pivotal role in hepatic angiotensinogen production in vivo. Hepatic angiotensinogen mRNA was decreased by the transfection of AGE 2 but not mismatched decoy ODN. Transfection of decoy but not mismatched ODN against AGE 2 resulted in a transient decrease in blood pressure of spontaneously hypertensive rats (SHR)...Continue Reading

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Citations

Dec 1, 2001·Pharmacology & Therapeutics·R MorishitaT Ogihara
Sep 27, 2000·Biochimica Et Biophysica Acta·L PenolazziR Piva
Nov 7, 1998·Clinical Chemistry and Laboratory Medicine : CCLM·R MorishitaT Ogihara
Mar 20, 2004·Expert Review of Cardiovascular Therapy·Naruya TomitaRyuichi Morishita
Jul 29, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ichiro OgushiJiro Fujimoto
Dec 7, 2007·International Journal of Cancer. Journal International Du Cancer·Haruhito AzumaYoji Katsuoka
Mar 22, 2005·Atherosclerosis·Maria M StollenwerkMikko P S Ares
Dec 1, 1996·Hypertension·V J Dzau, M Horiuchi
Mar 27, 2007·Clinical and Experimental Nephrology·Naruya TomitaRyuichi Morishita
Nov 2, 2018·PloS One·Alexander Perdomo-PantojaTalia Wegman-Ostrosky
Oct 31, 2014·World Journal of Gastroenterology : WJG·Kyung-Hyun Kim, Kwan-Kyu Park
Aug 5, 1998·The American Journal of Physiology·K TamuraM Ishii
Oct 11, 2001·American Journal of Physiology. Renal Physiology·Z Z Yang, A P Zou

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