Atrial natriuretic peptide is negatively regulated by microRNA-425

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 bloo...

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Veröffentlicht in:The Journal of clinical investigation 2013-08, Vol.123 (8), p.3378-3382
Hauptverfasser: 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
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container_issue 8
container_start_page 3378
container_title The Journal of clinical investigation
container_volume 123
creator 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
description 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.
doi_str_mv 10.1172/JCI67383
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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. 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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.</description><subject>3' Untranslated Regions</subject><subject>Adult</subject><subject>Animals</subject><subject>Atrial Natriuretic Factor - blood</subject><subject>Atrial Natriuretic Factor - genetics</subject><subject>Biomedical research</subject><subject>Blood pressure</subject><subject>Brief Report</subject><subject>Cardiovascular disease</subject><subject>Care and treatment</subject><subject>Cercopithecus aethiops</subject><subject>COS Cells</subject><subject>Cyclic GMP - blood</subject><subject>Diet</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Gene Frequency</subject><subject>Genealogy</subject><subject>Genetic aspects</subject><subject>Genetic Association Studies</subject><subject>Genetic variation</subject><subject>Genotype &amp; phenotype</subject><subject>Heart failure</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypertension - blood</subject><subject>Hypertension - genetics</subject><subject>Male</subject><subject>MicroRNA</subject><subject>MicroRNAs - genetics</subject><subject>Natriuretic peptides</subject><subject>Nutrition research</subject><subject>Peptides</subject><subject>Polymorphism, Single Nucleotide</subject><subject>RNA Interference</subject><subject>Sequence Analysis, DNA</subject><subject>Sodium Chloride, Dietary - pharmacology</subject><subject>Studies</subject><subject>Young Adult</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkttq3DAQhk1paTZpoU9QDIXSXjjV0ZJvAtulhy2hgfRwK2Tt2KvglbeWHLJv3wndpHHZi6KLgZlPv0Yzf5a9oOSUUsXefVksS8U1f5TNqJS60Izrx9mMEEaLCgtH2XGMV4RQIaR4mh1huVQl47Ps_TwN3nZ5sBjHAZJ3-Ra2ya8g9zEP0Nrkr6Hb5QO0Y2cTrPJ6l2-8G_rLr_NCMPkse9LYLsLzfTzJfnz88H3xuTi_-LRczM8LpwhPhSaaSFZJ7mxda-G0whZWTgktm7qRrOSuqhVphMBs5RSzlFQaVs4Caxh3_CQ7-6O7HesN5iGkwXZmO_iNHXamt95MK8GvTdtfG65YSWWFAm_2AkP_a4SYzMZHB11nA_RjNFRwQThhvET01T_oVT8OAb-HFNMVDo9Wf6nWdmB8aHp8192KmjkXCCjJKVLFAaqFANhkH6DxmJ7wpwd4PCvAsR-88HZyAZkEN6m1Y4xm-e3y_9mLn1P29QN2DbZL69h3Y_J9iFNwP1g0RYwDNPdLocTcGtTcGRTRlw-XeA_eOZL_Bvuf2mc</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>Arora, Pankaj</creator><creator>Wu, Connie</creator><creator>Khan, Abigail May</creator><creator>Bloch, Donald B</creator><creator>Davis-Dusenbery, Brandi N</creator><creator>Ghorbani, Anahita</creator><creator>Spagnolli, Ester</creator><creator>Martinez, Andrew</creator><creator>Ryan, Allicia</creator><creator>Tainsh, Laurel T</creator><creator>Kim, Samuel</creator><creator>Rong, Jian</creator><creator>Huan, Tianxiao</creator><creator>Freedman, Jane E</creator><creator>Levy, Daniel</creator><creator>Miller, Karen K</creator><creator>Hata, Akiko</creator><creator>Del Monte, Federica</creator><creator>Vandenwijngaert, Sara</creator><creator>Swinnen, Melissa</creator><creator>Janssens, Stefan</creator><creator>Holmes, Tara M</creator><creator>Buys, Emmanuel S</creator><creator>Bloch, Kenneth D</creator><creator>Newton-Cheh, Christopher</creator><creator>Wang, Thomas J</creator><general>American Society for Clinical Investigation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7T5</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20130801</creationdate><title>Atrial natriuretic peptide is negatively regulated by microRNA-425</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c703t-808052953cabb84c87676dc7485fbf5263c9b70f446dc9c72a1098edcae2f23c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3' Untranslated Regions</topic><topic>Adult</topic><topic>Animals</topic><topic>Atrial Natriuretic Factor - blood</topic><topic>Atrial Natriuretic Factor - genetics</topic><topic>Biomedical research</topic><topic>Blood pressure</topic><topic>Brief Report</topic><topic>Cardiovascular disease</topic><topic>Care and treatment</topic><topic>Cercopithecus aethiops</topic><topic>COS Cells</topic><topic>Cyclic GMP - blood</topic><topic>Diet</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Gene Frequency</topic><topic>Genealogy</topic><topic>Genetic aspects</topic><topic>Genetic Association Studies</topic><topic>Genetic variation</topic><topic>Genotype &amp; 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source Journals@Ovid Ovid Autoload; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection
subjects 3' Untranslated Regions
Adult
Animals
Atrial Natriuretic Factor - blood
Atrial Natriuretic Factor - genetics
Biomedical research
Blood pressure
Brief Report
Cardiovascular disease
Care and treatment
Cercopithecus aethiops
COS Cells
Cyclic GMP - blood
Diet
Female
Gene expression
Gene Expression - drug effects
Gene Frequency
Genealogy
Genetic aspects
Genetic Association Studies
Genetic variation
Genotype & phenotype
Heart failure
Humans
Hypertension
Hypertension - blood
Hypertension - genetics
Male
MicroRNA
MicroRNAs - genetics
Natriuretic peptides
Nutrition research
Peptides
Polymorphism, Single Nucleotide
RNA Interference
Sequence Analysis, DNA
Sodium Chloride, Dietary - pharmacology
Studies
Young Adult
title Atrial natriuretic peptide is negatively regulated by microRNA-425
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