title: Atrial natriuretic peptide is negatively regulated by microRNA-425.
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.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Arora
authors.forename: Connie
authors.initials: C
authors.lastname: Wu
authors.forename: Abigail May
authors.initials: AM
authors.lastname: Khan
authors.forename: Donald B
authors.initials: DB
authors.lastname: Bloch
authors.forename: Brandi N
authors.initials: BN
authors.lastname: Davis-Dusenbery
authors.forename: Anahita
authors.initials: A
authors.lastname: Ghorbani
authors.forename: Ester
authors.initials: E
authors.lastname: Spagnolli
authors.forename: Andrew
authors.initials: A
authors.lastname: Martinez
authors.forename: Allicia
authors.initials: A
authors.lastname: Ryan
authors.forename: Laurel T
authors.initials: LT
authors.lastname: Tainsh
authors.forename: Samuel
authors.initials: S
authors.lastname: Kim
authors.forename: Jian
authors.initials: J
authors.lastname: Rong
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Huan
authors.forename: Jane E
authors.initials: JE
authors.lastname: Freedman
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Karen K
authors.initials: KK
authors.lastname: Miller
authors.forename: Akiko
authors.initials: A
authors.lastname: Hata
authors.forename: Federica
authors.initials: F
authors.lastname: Del Monte
authors.forename: Sara
authors.initials: S
authors.lastname: Vandenwijngaert
authors.forename: Melissa
authors.initials: M
authors.lastname: Swinnen
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
authors.forename: Tara M
authors.initials: TM
authors.lastname: Holmes
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood* / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; C555677:MIRN425 microRNA, human; D035683:MicroRNAs; C472955:NPPA protein, human; D017673:Sodium Chloride, Dietary; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP