Atrial natriuretic peptide is negatively regulated by microRNA-425

Pankaj Arora, Connie Wu, Abigail May 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 SwinnenStefan Janssens, Tara M. Holmes, Emmanuel S. Buys, Kenneth D. Bloch, Christopher Newton-Cheh, Thomas J. Wang

Research output: Contribution to journalArticle

80 Scopus citations

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

ASJC Scopus subject areas

  • Medicine(all)

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    Arora, P., Wu, C., May Khan, A., Bloch, D. B., Davis-Dusenbery, B. N., Ghorbani, A., Spagnolli, E., Martinez, A., Ryan, A., Tainsh, L. T., Kim, S., Rong, J., Huan, T., Freedman, J. E., Levy, D., Miller, K. K., Hata, A., Del Monte, F., Vandenwijngaert, S., ... 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