Atrial natriuretic peptide is negatively regulated by microRNA-425

作者：Arora Pankaj; Wu Connie; Khan Abigail May; 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

来源：Journal of Clinical Investigation, 2013, 123(8): 3378-3382.

DOI：10.1172/JCI67383

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.

• 出版日期2013-8