Atrial natriuretic peptide is negatively regulated by microRNA-425

Pankaj Arora, Connie Wu, Abigail Khan, Donald B. Bloch, Brandi N. Davis-Dusenbery, Anahita Ghorbani, Ester Spagnolli, Andrew Martinez, Allicia Ryan, Laurel T. Tainsh, Samuel Kim, Jian Rong, Tianxiao Huan, Jane E. Freedman, Daniel Levy, Karen K. Miller, Akiko Hata, Federica Del Monte, Sara Vandenwijngaert, Melissa Swinnen & 6 others Stefan Janssens, Tara M. Holmes, Emmanuel S. Buys, Kenneth D. Bloch, Christopher Newton-Cheh, Thomas J. Wang

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3? untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.

Original languageEnglish (US)
Pages (from-to)3378-3382
Number of pages5
JournalJournal of Clinical Investigation
Volume123
Issue number8
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

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Atrial Natriuretic Factor
MicroRNAs
Salts
Alleles
Diet
Genotype
Blood Pressure
Untranslated Regions
Brain Natriuretic Peptide
Intravenous Infusions
Individuality
Heart Failure
Hypertension
Messenger RNA
Population
Genes
N-propionylprocainamide

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Arora, P., Wu, C., Khan, A., Bloch, D. B., Davis-Dusenbery, B. N., Ghorbani, A., ... Wang, T. J. (2013). Atrial natriuretic peptide is negatively regulated by microRNA-425. Journal of Clinical Investigation, 123(8), 3378-3382. https://doi.org/10.1172/JCI67383

Atrial natriuretic peptide is negatively regulated by microRNA-425. / Arora, Pankaj; Wu, Connie; Khan, Abigail; Bloch, Donald B.; Davis-Dusenbery, Brandi N.; Ghorbani, Anahita; Spagnolli, Ester; Martinez, Andrew; Ryan, Allicia; Tainsh, Laurel T.; Kim, Samuel; Rong, Jian; Huan, Tianxiao; Freedman, Jane E.; Levy, Daniel; Miller, Karen K.; Hata, Akiko; Del Monte, Federica; Vandenwijngaert, Sara; Swinnen, Melissa; Janssens, Stefan; Holmes, Tara M.; Buys, Emmanuel S.; Bloch, Kenneth D.; Newton-Cheh, Christopher; Wang, Thomas J.

In: Journal of Clinical Investigation, Vol. 123, No. 8, 01.08.2013, p. 3378-3382.

Research output: Contribution to journalArticle

Arora, P, Wu, C, Khan, A, Bloch, DB, Davis-Dusenbery, BN, Ghorbani, A, Spagnolli, E, Martinez, A, Ryan, A, Tainsh, LT, Kim, S, Rong, J, Huan, T, Freedman, JE, Levy, D, Miller, KK, Hata, A, Del Monte, F, Vandenwijngaert, S, Swinnen, M, Janssens, S, Holmes, TM, Buys, ES, Bloch, KD, Newton-Cheh, C & Wang, TJ 2013, 'Atrial natriuretic peptide is negatively regulated by microRNA-425', Journal of Clinical Investigation, vol. 123, no. 8, pp. 3378-3382. https://doi.org/10.1172/JCI67383
Arora P, Wu C, Khan A, Bloch DB, Davis-Dusenbery BN, Ghorbani A et al. Atrial natriuretic peptide is negatively regulated by microRNA-425. Journal of Clinical Investigation. 2013 Aug 1;123(8):3378-3382. https://doi.org/10.1172/JCI67383
Arora, Pankaj ; Wu, Connie ; Khan, Abigail ; Bloch, Donald B. ; Davis-Dusenbery, Brandi N. ; Ghorbani, Anahita ; Spagnolli, Ester ; Martinez, Andrew ; Ryan, Allicia ; Tainsh, Laurel T. ; Kim, Samuel ; Rong, Jian ; Huan, Tianxiao ; Freedman, Jane E. ; Levy, Daniel ; Miller, Karen K. ; Hata, Akiko ; Del Monte, Federica ; Vandenwijngaert, Sara ; Swinnen, Melissa ; Janssens, Stefan ; Holmes, Tara M. ; Buys, Emmanuel S. ; Bloch, Kenneth D. ; Newton-Cheh, Christopher ; Wang, Thomas J. / Atrial natriuretic peptide is negatively regulated by microRNA-425. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 8. pp. 3378-3382.
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AU - Wu, Connie

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AU - Ghorbani, Anahita

AU - Spagnolli, Ester

AU - Martinez, Andrew

AU - Ryan, Allicia

AU - Tainsh, Laurel T.

AU - Kim, Samuel

AU - Rong, Jian

AU - Huan, Tianxiao

AU - Freedman, Jane E.

AU - Levy, Daniel

AU - Miller, Karen K.

AU - Hata, Akiko

AU - Del Monte, Federica

AU - Vandenwijngaert, Sara

AU - Swinnen, Melissa

AU - Janssens, Stefan

AU - Holmes, Tara M.

AU - Buys, Emmanuel S.

AU - Bloch, Kenneth D.

AU - Newton-Cheh, Christopher

AU - Wang, Thomas J.

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N2 - Numerous common genetic variants have been linked to blood pressure, but no underlying mechanism has been elucidated. Population studies have revealed that the variant rs5068 (A/G) in the 3? untranslated region of NPPA, the gene encoding atrial natriuretic peptide (ANP), is associated with blood pressure. We selected individuals on the basis of rs5068 genotype (AG vs. AA) and fed them a low- or high-salt diet for 1 week, after which they were challenged with an intravenous saline infusion. On both diets, before and after saline administration, ANP levels were up to 50% higher in AG individuals than in AA individuals, a difference comparable to the changes induced by high-salt diet or saline infusion. In contrast, B-type natriuretic peptide levels did not differ by rs5068 genotype. We identified a microRNA, miR-425, that is expressed in human atria and ventricles and is predicted to bind the sequence spanning rs5068 for the A, but not the G, allele. miR-425 silenced NPPA mRNA in an allele-specific manner, with the G allele conferring resistance to miR-425. This study identifies miR-425 as a regulator of ANP production, raising the possibility that miR-425 antagonists could be used to treat disorders of salt overload, including hypertension and heart failure.

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